[Application of rectal suppository vitaprost plus before and after transurethral resection of the prostate].
An open prospective study aimed to assessment the efficacy of a new formulation--rectal suppository vitaprost plus--compared with the standard antibacterial prevention of infectious and inflammatory complications and irritative disorders after transurethral resection of the prostate (TURP) was performed. From January to November 2011, TURP for prostatic adenoma was performed in 73 patients. Patients were randomized into two groups. The study group received rectal suppositories vitaprost plus once a day as a prophylactic antibacterial therapy before and after surgery, control group--pefloxacin 400 mg 2 times a day. Both groups began taking the drug in the morning before surgery. Duration of antibiotic therapy was 10 days in both groups. In the study group, hyperthermia over 37.5 degrees C in the 1st postoperative day was observed in 13 (43%) patients, in the control group--in 16 patients (53%). Cancellation of antibacterial treatment was required in four patients of the study group. There was no discontinuation of treatment due to adverse reactions in any case. In all patients, cancellation of drug treatment has been associated with the development of febrile hyperthermia in the presence of clinical need for catheter deployment, which required a change of antibacterial therapy. In the study group this parameter was 13% versus 37% in control group (P < 0.05). No significant differences in objective parameters (maximum urinary flow rate, residual urine volume, prostate volume) were registered. However, a statistically significant reduction in subjective parametres (IPSS and QoL scores) in the study group (11.5 +/- 1.2 and 2.6 +/- 0.3 points, respectively) compared with controls (15.5 +/- 1.4 and 3.8 +/- 0.5 points, respectively) was observed.


Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study).
To compare the efficacy and safety between tocilizumab added to methotrexate and tocilizumab switched from methotrexate in patients with active rheumatoid arthritis (RA). This is a 2-year randomised, controlled study. RA patients with moderate or high disease activity despite methotrexate were randomly assigned either to tocilizumab added to methotrexate (add-on) or tocilizumab switched from methotrexate (switch). The primary endpoint was the DAS28 remission rate at week 24. Secondary objectives included other clinical efficacy indices, radiological outcomes assessed with the van der Heijde-modified total Sharp scoring system (mTSS), and safety. Of 223 randomised patients, 83% completed 52 weeks. DAS28 remission rates at week 24 were 70% for add-on and 55% for switch (p=0.02), but they became comparable at week 52 (72% vs 70%, p=0.86). Structural remission rates (mTSS≤0.5) at week 52 were not different (66% vs 64%, p=0.92). However, clinically relevant radiographic progression rates (CRRP; mTSS≥3) tended to be higher with the switch than with the add-on (15% vs 7%, p=0.07). Radiographic progression in the CRRP patients was larger with the switch than with the add-on (9.0/year vs 5.0/year, p=0.04). The difference in the mean C-reactive protein of the CRRP patients was significant for the first 24 weeks (1.56 vs 0.49, p=0.001) but not for the following 28 weeks (0.10 vs 0.04, p=0.1). Overall safety was preferable in the switch group. In RA patients with inadequate response to methotrexate, tocilizumab added to methotrexate more rapidly suppressed inflammation than tocilizumab switched from methotrexate, leading to superior clinical efficacy and prevention of joint destruction. NCT01120366.


Heart failure related cardiogenic shock: An ISHLT consensus conference content summary.
In recent years, there have been significant advancements in the understanding, risk-stratification, and treatment of cardiogenic shock (CS). Despite improved pharmacologic and device-based therapies for CS, short-term mortality remains as high as 50%. Most recent efforts in research have focused on CS related to acute myocardial infarction, even though heart failure related CS (HF-CS) accounts for >50% of CS cases. There is a paucity of high-quality evidence to support standardized clinical practices in approach to HF-CS. In addition, there is an unmet need to identify disease-specific diagnostic and risk-stratification strategies upon admission, which might ultimately guide the choice of therapies, and thereby improve outcomes and optimize resource allocation. The heterogeneity in defining CS, patient phenotypes, treatment goals and therapies has resulted in difficulty comparing published reports and standardized treatment algorithms. An International Society for Heart and Lung Transplantation (ISHLT) consensus conference was organized to better define, diagnose, and manage HF-CS. There were 54 participants (advanced heart failure and interventional cardiologists, cardiothoracic surgeons, critical care cardiologists, intensivists, pharmacists, and allied health professionals), with vast clinical and published experience in CS, representing 42 centers worldwide. State-of-the-art HF-CS presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues, including but not limited to models of CS care delivery, patient presentations in HF-CS, and strategies in HF-CS management. This consensus report summarizes the contemporary literature review on HF-CS presented in the first half of the conference (part 1), while the accompanying document (part 2) covers the breakout sessions where the previously agreed upon clinical issues were discussed with an aim to get to a consensus.


'Sharing things with people that I don't even know': help-seeking for psychological symptoms in injured Black men in Philadelphia.
Objectives: Psychological distress is common in survivors of traumatic injury, yet across United States' trauma systems, it is rare that standard injury care integrates psychological evaluation and professional mental healthcare. The purpose of this study was to explore help-seeking for psychological symptoms in injured Black men living in Philadelphia. Design: A subset of a cohort of 551 injured Black men admitted to a Trauma Center in Philadelphia participated in qualitative interviews that explored their perceptions of psychological symptoms after injury and the factors that guided their decision to seek professional mental health help. Data from 32 participants were analyzed for narrative and thematic content. Results: Three overarching themes emerged: (1) facilitators of help-seeking, (2) barriers to help-seeking, and (3) factors underlying the decision not to consider professional help. Five participants felt that their injury-related psychological distress was severe enough to merit professional help despite any perceived barriers. Seventeen participants identified systemic and interpersonal obstacles to professional help that prevented them from seeking this kind of care. These included: financial constraints, limited access to mental healthcare services, and fear of the judgments of mental healthcare professionals. Ten participants would not consider professional help; these men perceived a lack of need and sufficiency in their existing social support networks. Conclusions: Research is needed to inform or identify interventions that diminish the impact of barriers to care, and identify from whom, where, and how professional mental health help might be more effectively offered to injured Black men in recovery environments like Philadelphia.


Sickle cell trait, malaria and anaemia in Zambian pregnant women.
IN a sample of 424 Zambian pregnant women a series of tests were made: sickle cell test, haemoglobin and packed cell volume estimations and screening of a thick blood smear for malaria and a thin blood smear for the presence of signs of anaemia. More anaemia was found in the primigravidae than in the multigravidae. The Hb-level was found to be lower with primigravidity and independently of this gravidity effect, also with malaria. Taking into account the higher malaria frequency in primigravidae, this group must be considered as a high risk group for the development of anaemia. The presence of the sickle cell trait was shown to have no effect on anaemia and malaria. In addition to the tests during pregnancy, the placentae and umbilical cords of 155 women were screened for malaria, as were the mothers just before delivery. More malaria parasites were detected in the placenta of the primiparous as compared with the multiparous women. Peripheral parasitaemia was strikingly less prevalent than infestation of the placenta.


Malignant Melanomas of the Skin Arising on the Feet.
Cutaneous melanoma frequently develops on the lower limbs, but rarely on the feet, in people with light skin. By contrast, the feet are one of the most frequently affected sites in people with dark skin. This study assessed the prevalence and clinico-pathological findings of biopsy-proven skin melanomas that were diagnosed over 11 years. The study group comprised 217 primary melanomas from 210 patients. Eight (3.7%) melanomas were located on the feet. These were all invasive and obtained from 8 patients (5 females and 3 males) aged 56-85 years (mean age 72 years). In general, the lesions were large (mean diameter 3.5cm) and had a high Breslow index (mean thickness 5.6mm). They were all ulcerated, and some invaded deep into the subcutaneous tissue. Histologic analyses demonstrated that three tumors exhibited features of acral lentiginous melanoma, two were nodular melanomas, and one was a superficial spreading melanoma. Two cases could not be histologically classified. Although skin melanomas arising on the feet are relatively rare in our ethnicity, they are usually bioptically diagnosed at an advanced stage. Such melanomas may initially imitate other pathologic entities. Therefore, this location should not be overlooked during the medical workup, and melanoma should be suspected when patients present with non-healing defects or local pigmented changes on the soles of the feet or toes. Key words: malignant melanoma - anatomic distribution - foot The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 9. 2. 2018 Accepted: 16. 5. 2018.


Application of student's t-test, analysis of variance, and covariance.
Student's t test (t test), analysis of variance (ANOVA), and analysis of covariance (ANCOVA) are statistical methods used in the testing of hypothesis for comparison of means between the groups. The Student's t test is used to compare the means between two groups, whereas ANOVA is used to compare the means among three or more groups. In ANOVA, first gets a common P value. A significant P value of the ANOVA test indicates for at least one pair, between which the mean difference was statistically significant. To identify that significant pair(s), we use multiple comparisons. In ANOVA, when using one categorical independent variable, it is called one-way ANOVA, whereas for two categorical independent variables, it is called two-way ANOVA. When using at least one covariate to adjust with dependent variable, ANOVA becomes ANCOVA. When the size of the sample is small, mean is very much affected by the outliers, so it is necessary to keep sufficient sample size while using these methods.


Low nucleotide diversity in man.
The nucleotide diversity (pi) in humans is studied by using published cDNA and genomic sequences that have been carefully checked for sequencing accuracy. This measure of genetic variability is defined as the number of nucleotide differences per site between two randomly chosen sequences from a population. A total of more than 75,000 base pairs from 49 loci are compared. The DNA regions studied are the 5' and 3' untranslated regions and the amino acid coding regions. The coding regions are divided into nondegenerate sites (i.e., sites at which all possible changes are nonsynonymous), twofold degenerate sites (i.e., sites at each of which one of the three possible changes is synonymous) and fourfold degenerate sites (i.e., sites at which all three possible changes are synonymous). The pi values estimated are, respectively, 0.03 and 0.04% for the 5' and 3' UT regions, and 0.03, 0.06 and 0.11% for nondegenerate, twofold degenerate and fourfold degenerate sites. Since the highest pi value is only 0.11%, which is about one order of magnitude lower than those in Drosophila populations, the nucleotide diversity in humans is very low. The low diversity is probably due to a relatively small long-term effective population size rather than any severe bottleneck during human evolution.


Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update.
Purpose To update, in collaboration with Cancer Care Ontario (CCO), key recommendations of the American Society of Clinical Oncology (ASCO) guideline on the role of bone-modifying agents (BMAs) in metastatic breast cancer. This focused update addressed the new data on intervals between dosing and the role of BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted targeted systematic literature reviews to identify relevant studies. Results The Update Committee reviewed three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of BMAs, and two randomized trials of BMAs in control of pain secondary to bone metastases. Recommendations Patients with breast cancer who have evidence of bone metastases should be treated with BMAs. Options include denosumab, 120 mg subcutaneously, every 4 weeks; pamidronate, 90 mg intravenously, every 3 to 4 weeks; or zoledronic acid, 4 mg intravenously every 12 weeks or every 3 to 4 weeks. The analgesic effects of BMAs are modest, and they should not be used alone for bone pain. The Update Committee recommends that the current standard of care for supportive care and pain management-analgesia, adjunct therapies, radiotherapy, surgery, systemic anticancer therapy, and referral to supportive care and pain management-be applied. Evidence is insufficient to support the use of one BMA over another. Additional information is available at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .


Increased incidence of cardiac complications in kidney transplant recipients with cytomegalovirus disease.
The transplant literature has not shown cytomegalovirus (CMV) disease to be a significant risk factor for posttransplant cardiac complications. A large number of nontransplant studies have, however, reported an association between coronary heart disease (CHD) and CMV disease. Pathology studies have demonstrated a high incidence of CMV in atheromatous plaques from the coronary circulation. We performed multivariate analysis to determine if posttransplant CMV disease was a significant risk factor for cardiac complications in kidney transplant recipients. We also performed univariate analysis to determine which cardiac complications were more common in the recipients with CMV disease. Between January 1, 1984 and June 30, 1997, 1859 adults underwent kidney transplants at our institution. Of these, 377 developed one of the following cardiac complications posttransplant: myocardial infarction, angina, arrhythmia, congestive heart failure, and angiographic vessel occlusion. By multivariate analysis, significant risk factors for one of the above cardiac complications were recipient age >50 years [odds ratio (OR)=2.5, P=0.0001], diabetes (OR=1.99, P=0.0001), a history of cardiac disease pretransplant (OR= 1.34, P=0.04), and CMV disease (OR=1.5, P=0.01). Univariate analysis demonstrated that recipients with CMV disease had a higher overall incidence of cardiac complications. Arrhythmias, congestive heart failure, and vessel occlusion were more common in those with CMV disease. The incidence of myocardial infarction, angina, and cardiac arrest did not differ between the two groups (recipients with versus without CMV disease). CMV disease is associated with an increased risk of cardiac complications in kidney transplant recipients. In our series, angiographic vessel occlusion was more common in recipients with CMV disease. This interesting finding may support the theory that CMV plays some role in the pathogenesis of CHD.


Client-centered counseling and facilitation in improving modern contraceptive uptake in urban slum of Karachi Pakistan.
Population growth in Pakistan necessitates the implementation of comprehensive family planning (FP) initiatives. The adoption of modern contraceptives, especially long-acting reversible contraceptives (LARC), and permanent family planning methods in the country is challenging and has yet to reach an optimal level. These challenges are deeply rooted in the lack of informed decision-making, as well as demographic and maternal obstetric history. Interventions tailored according to women's needs can address the challenges faced by FP programs. This paper presents the findings of the implementation of a client-centered counseling and facilitation approach in an urban slum in Karachi, Pakistan. Such an approach has the potential to inform women and help them make better decisions regarding their health. In Rehri Goth, a slum located in Karachi, client-centered counseling along with facilitation at the facility was implemented to encourage the adoption of any modern contraceptive methods, with a specific emphasis on promoting the use of LARCs and permanent methods (where needed) among married women of reproductive age (MWRA). This approach was integrated into the existing Maternal, Neonatal, and Child Health (MNCH) services established in 2014. During the routine delivery of services, data were collected on various aspects including demographic characteristics, obstetric history, motivation to adopt LARCs, and reasons for refusal. A total of N = 3079 eligible MWRA received client-centered counseling, and 60.3% accepted modern contraceptive methods after counseling. Furthermore, 32.5% of these MWRA adopted LARCs or permanent methods. Factors explaining reluctance to adopt any method by MWRA despite specialized counselling were: age >25 years (AOR:1.28, 95% CI:1.08-1.51), no formal education (AOR:1.58, 95% CI:1.36-1.89), having no decision making role at household (AOR:1.60, 95% CI:1.36-1.89), the desire of female or male progeny (AOR:1.86, 95% CI:1.59-2.25) and age of youngest alive ≥3 years (AOR:1.50, 95% CI:1.22-1.84). Factors explaining adoption of short-term methods instead of LARCs or permanent method were: being resident in high under-five mortality clusters (AOR:1.56, 95% CI:1.14-2.14), maternal age > 25 years (AOR:1.88, 95% CI: 1.47-2.40), no decision-making role (AOR:11.19, 95% CI:8.74-14.34), no history of abortions (AOR:2.59, 95% CI:1.79-3.75), no female child (AOR:1.85, 95% CI:1.30-2.65) and ≤ 2 children (AOR:1.74, 95% CI:1.08-2.81). Considering the obstacles mothers face when it comes to accessing extended contraception, public health officials can devise effective strategies that empower MWRA to make well-informed and empowered choices regarding their families and reproductive health.


Parental fears following their child's brain tumor diagnosis and treatment.
The objective of this study is to portray the illness-related threats experienced by parents of children after the diagnosis of central nervous system (CNS) tumor. Parents were asked to rate the extent to which they experienced a set of specific fears related to their child's brain tumor and its treatment. Outcomes for parents of CNS tumor patients (n = 82) were compared with those of reference parents of patients treated for acute lymphoblastic leukemia (n = 208). The fears about an illness recurrence and the late effects of treatment were most prominent among parents of CNS tumor patients. For 7 out of 11 kinds of fear, parents of CNS tumor patients expressed a stronger fear than the reference group. More than a quarter of the parents of children treated for CNS tumors feared a complete decline of the child. Parents of CNS tumor patients experience relatively heightened cancer related fears in several domains. The fear of devastating consequences felt by one fourth of parents signals the need of individualized psychological support and information at diagnosis and follow-up to facilitate parental coping with the posttreatment situation.


Inhibitory action of 10-deazaaminopterins and their polyglutamates on human thymidylate synthase.
The action of 10-deazaaminopterin, its 10-alkyl derivatives, and their polyglutamates against thymidylate synthase (TMPS) from human acute myeloblastic leukemia was examined. Comparison of aminopterin with methotrexate showed that the methylation of the N10-position (methotrexate) increased the inhibitory effect of aminopterin on TMPS. In contrast, alkylation of the 10-position of 10-deazaaminopterin decreased inhibition of TMPS, and the 50% inhibitory concentration values were progressively higher, in the order 10,10-dimethyl-, 10-methyl-, and 10-ethyl-derivatives. The addition of gamma-glutamyl moieties to both 10-deazaaminopterin, and one of its alkylated analogs, 10-ethyl-10-deazaaminopterin, enhanced inhibition. The maximum inhibition was achieved with the addition of three glutamyl moieties to 10-deazaaminopterin and two glutamyl moieties to 10-ethyl-10-deazaaminopterin, respectively. Thus, 10-deazaaminopterin-tetraglutamate was 138-fold and 10-ethyl-10-deazaaminopterin-triglutamate was greater than 51-fold more active than their respective parental compound. The compounds 10-deazaaminopterin and its polyglutamates, 10-methyl- and 10,10-dimethyl-analogs, inhibited TMPS in a noncompetitive fashion with respect to 5,10-methylene-tetrahydropteroylglutamate. Ki values for the monoglutamates were 220 microM, 310 microM, and 225 microM, respectively. In contrast, 10-ethyl-10-deazaaminopterin and its polyglutamates inhibited TMPS in a competitive fashion with a Ki value of 410 microM for the monoglutamate. With 5,10-methylene-tetrahydropteroylpentaglutamate as a substrate, 10-deazaaminopterin and its polyglutamates behaved as mixed type inhibitors, and 10-ethyl-10-deazaaminopterin, monoglutamate and diglutamate, behaved as noncompetitive inhibitors, whereas its pentaglutamate behaved as a mixed-type inhibitor. These results suggest that the addition of gamma-glutamyl moieties to the substrate also caused the change in the mode of inhibitory action of these compounds. These findings also show that both replacement of the N10-position of the 4-aminopteroyl structure with a methylene group and its alkylation caused interesting and unexpected changes in the structure-activity relationships and the mode of action for these 4-aminopteroyl antifolates as inhibitors of TMPS, which may be therapeutically relevant.


Contextual variations in associations between measures of aggression and withdrawal and functioning with peers: A replication study.
Data from 790 older school-age (Mage = 10.2 years, SD = 1.2 years) girls (N = 427) and boys from Barranquilla, Colombia (N = 449) and Montréal, Canada (N = 331) were used to replicate findings reported by Valdivia et al. (2005). This prior study revealed contextual variations in the association between two measures of social behavior, specifically aggression and withdrawal, and two measures of effective functioning with peers, specifically sociometric preference and friendship. The Montréal participants were primarily from families with European backgrounds. The ethnicity of the participants from Barranquilla can be described as Latinx/Caribbean. Multilevel analyses provided evidence of replication of place differences only for the associations between measures of aggression and sociometric preference. Stronger negative associations were observed between (a) measures of aggression and sociometric preference, (b) measures of withdrawal and sociometric preference, and (c) withdrawal and friendship in peer groups that were high in collectivism. These findings are interpreted as largely replicating the deep structure of the findings from the Valdivia et al. study. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Integrated sensing and processing decision trees.
We introduce a methodology for adaptive sequential sensing and processing in a classification setting. Our objective for sensor optimization is the back-end performance metric--in this case, misclassification rate. Our methodology, which we dub Integrated Sensing and Processing Decision Trees (ISPDT), optimizes adaptive sequential sensing for scenarios in which sensor and/or throughput constraints dictate that only a small subset of all measurable attributes can be measured at any one time. Our decision trees optimize misclassification rate by invoking a local dimensionality reduction-based partitioning metric in the early stages, focusing on classification only in the leaves of the tree. We present the ISPDT methodology and illustrative theoretical, simulation, and experimental results.


Cross-sectional associations between the screen-time of parents and young children: differences by parent and child gender and day of the week.
Greater time spent screen-viewing (SV) has been linked to adverse health outcomes. The aim of this study was to examine whether parental SV time is associated with child SV time on week and weekend days. Cross-sectional survey of 1078 children aged 5-6 and at least 1 parent. Child and parent SV was reported for weekday and weekend days. Logistic regression examined whether parental SV time was associated with child SV time, with separate analyses for mothers and fathers and interaction terms for child gender. 12% of boys, 8% of girls and 30% of mothers and fathers watched ≥ 2 hours of TV each weekday. On a weekend day, 45% of boys, 43% of girls, 53% of mothers and 57% of fathers spent ≥ 2 hours watching TV. Where parents exceeded 2 hours TV-watching per weekday, children were 3.4 times more likely to spend ≥ 2 hours TV-watching if their father exceeded the threshold with odds of 3.7 for mothers. At weekends, daughters of fathers who exceeded 2 hours watching TV were over twice as likely as sons to exceed this level. Evidence that parent time spent using computers was associated with child computer use was also strongest between fathers and daughters (vs. sons) (OR 3.5 vs. 1.0, p interaction=0.027). Strong associations were observed between parent and child SV and patterns were different for weekdays versus weekend days. Results show that time spent SV for both parents is strongly associated with child SV, highlighting the need for interventions targeting both parents and children.


Enzymatic isolation of cells from bone: cytotoxic enzymes of bacterial collagenase.
The enzymatic isolation of cells from fetal rat calvaria is most effectively achieved with crude Clostridium histolyticum collagenase. However, this bacterial collagenase damages the cells during the digestion of the tissue. We have used cell density, as measured by isopycnic centrifugation on polysucrose gradients, as an indicator of cell damage. There are at least two enzymes in crude bacterial collagenase capable of damaging the cells in this tissue. One of these is clostripain that has been well characterized. The other cytotoxic enzyme is uncharacterized, and its effects are not evident until the clostripain activity has been inhibited by alpha-tosyl-lysyl chloromethane. The apparent activity of this second enzyme can be inhibited by withholding magnesium from the digestion medium and by increasing the potassium concentration of the digestion medium.


Visualizing Antimicrobials in Bacterial Biofilms: Three-Dimensional Biochemical Imaging Using TOF-SIMS.
Bacterial biofilms are groups of bacteria that exist within a self-produced extracellular matrix, adhering to each other and usually to a surface. They grow on medical equipment and inserts such as catheters and are responsible for many persistent infections throughout the body, as they can have high resistance to many antimicrobials. Pseudomonas aeruginosa is an opportunistic pathogen that can cause both acute and chronic infections and is used as a model for research into biofilms. Direct biochemical methods of imaging of molecules in bacterial biofilms are of high value in gaining a better understanding of the fundamental biology of biofilms and biochemical gradients within them. Time of flight-secondary-ion mass spectrometry (TOF-SIMS) is one approach, which combines relatively high spatial resolution and sensitivity and can perform depth profiling analysis. It has been used to analyze bacterial biofilms but has not yet been used to study the distribution of antimicrobials (including antibiotics and the antimicrobial metal gallium) within biofilms. Here we compared two methods of imaging of the interior structure of P. aeruginosa in biological samples using TOF-SIMS, looking at both antimicrobials and endogenous biochemicals: cryosectioning of tissue samples and depth profiling to give pseudo-three-dimensional (pseudo-3D) images. The sample types included both simple biofilms grown on glass slides and bacteria growing in tissues in an ex vivo pig lung model. The two techniques for the 3D imaging of biofilms are potentially valuable complementary tools for analyzing bacterial infection. IMPORTANCE Modern analytical techniques are becoming increasingly important in the life sciences; imaging mass spectrometry offers the opportunity to gain unprecedented amounts of information on the distribution of chemicals in samples-both xenobiotics and endogenous compounds. In particular, simultaneous imaging of antibiotics (and other antimicrobial compounds) and bacterium-derived metabolites in complex biological samples could be very important in the future for helping to understand how sample matrices impact the survival of bacteria under antibiotic challenge. We have shown that an imaging mass spectrometric technique, TOF-SIMS, will be potentially extremely valuable for this kind of research in the future.


Effects of the food mutagens MeIQx and PhIP on the expression of cytochrome P450IA proteins in various tissues of male and female rats.
The promutagenic 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) found in cooked food are converted to their active forms mainly by cytochrome P450 forms IA1 and IA2. By induction of these isoenzymes the food mutagens could thus influence their own rate of activation. Male and female Wistar rats were given MeIQx, PhIP, beta-naphthoflavone (BNF) or saline i.p. at 50 mg/kg body wt on three consecutive days. On the fourth day the rats were killed and lungs, kidneys, liver and intestines taken. The microsomal fraction from each organ was prepared as well as 9000 g supernatant from the liver. The induction of cytochrome P450IA was measured at the protein level by enzymatic assays (ethoxyresorufin-O-deethylation, Ames' mutagenicity test) and immunoassays (Western blot) and at the pretranslational level by RNA hybridization (Northern blot). The binding affinities of MeIQx, PhIP and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-receptor were studied by evaluation of the competition with 3H-labelled TCDD for specific binding. Ethoxyresorufin-O-deethylase (EROD) activity was significantly increased in the liver (males 2.1-fold, females 3.3-fold), kidneys (males 2.1-fold, females 1.8-fold) and lungs (males 4.3-fold, females 3-fold) of the MeIQx-treated rats. Furthermore, the levels of cytochrome P450IA proteins were increased in these animals. It was not possible, however, to detect the corresponding mRNA. In the case of the PhIP-treated animals a significantly increased EROD activity (2.7-fold) and an increased cytochrome P450IA protein level were seen only in the male lungs. Only a very weak TCDD-receptor affinity was observed for PhIP, whereas MeIQx or IQ did not appear to compete significantly with [3H]TCDD for binding to the TCDD-receptor. It is concluded that MeIQx is a weak inducer of cytochrome P450IA in several organs of the rat, while PhIP induced these isoenzymes only in the male lungs. More work is needed to clarify the mechanism(s) whereby this induction occurs.


[Types of drug side effects and their classification].
The paper discusses side effects of the drugs and presents their classification, based on the principles of a pathogenetic approach. The classification includes side effects related to absolute and relative overdosage; specific effects, apart from the underlying one, related to the chemical structure, pharmacokinetics and pharmacodynamics; nonspecific effects due to individual features of the body.


[Chlamydia pneumoniae and vascular pathology].
An updating of the microbiological and diagnostic characteristics of Chlamydia pneumoniae is carried out, and a hypothesis formulated for its probable role in the production of the atheromatous plaque. Furthermore, the immunological results obtained from patients with peripheral vascular pathology, pneumonia from C. pneumoniae, or other genital processes from C. trachomatis, and a healthy control group are included. The presence of C. pneumoniae was revealed by PCR techniques in biopsies from patients with vascular pathology in a high percentage, particularly in samples from the carotid artery (74%) or the aortic wall (83%). The true pathogenic power of Chlamydia in vascular processes in questioned.


New strategies to improve exercise tolerance in chronic obstructive pulmonary disease.
Breathlessness is the most common symptom limiting exercise in patients with chronic obstructive pulmonary disease (COPD). Exercise training can improve both exercise tolerance and health status in these patients, intensity being of key importance. Nevertheless, in these patients extreme breathlessness and/or peripheral muscle fatigue may prevent patients from higher levels of intensity. In this review article the literature concerning the different ways to optimise exercise tolerance in patients with COPD, with the objective of enhancing the tolerance to higher exercise training intensity, is summarised. Continuous positive airway pressure and different modalities of noninvasive positive pressure ventilation (NPPV) may reduce breathlessness and increase exercise tolerance in these patients. Respiratory muscle unloading and reduction in intrinsic positive end-expiratory pressure have been considered among mechanisms underlying these effects. Nevertheless, the role of NPPV in pulmonary rehabilitation, if any, is still controversial. The addition of nocturnal domiciliary NPPV during a daily exercise programme in patients with severe COPD resulted in an improvement in exercise tolerance and quality of life. In patients with severe COPD application of electrical stimulation combined with active limb mobilisation significantly improved muscle strength, and interval training has been shown capable of inducing physiological training effects. Oxygen supplementation in patients who do not desaturate during exercise seems to be the most promising treatment, since it allows for higher exercise intensities and, therefore, superior training efficacy. In conclusion, further studies are needed to define the appropriate patients in order to generalise such interventions. The modalities discussed should be used as adjuncts to a well designed comprehensive respiratory rehabilitation programme.


Functional differentiation of a clone resembling embryonic cortical interneuron progenitors.
We have generated clones (L2.3 and RG3.6) of neural progenitors with radial glial properties from rat E14.5 cortex that differentiate into astrocytes, neurons, and oligodendrocytes. Here, we describe a different clone (L2.2) that gives rise exclusively to neurons, but not to glia. Neuronal differentiation of L2.2 cells was inhibited by bone morphogenic protein 2 (BMP2) and enhanced by Sonic Hedgehog (SHH) similar to cortical interneuron progenitors. Compared with L2.3, differentiating L2.2 cells expressed significantly higher levels of mRNAs for glutamate decarboxylases (GADs), DLX transcription factors, calretinin, calbindin, neuropeptide Y (NPY), and somatostatin. Increased levels of DLX-2, GADs, and calretinin proteins were confirmed upon differentiation. L2.2 cells differentiated into neurons that fired action potentials in vitro, and their electrophysiological differentiation was accelerated and more complete when cocultured with developing astroglial cells but not with conditioned medium from these cells. The combined results suggest that clone L2.2 resembles GABAergic interneuron progenitors in the developing forebrain.


Estimated daily salt intake in relation to blood pressure and blood lipids: the role of obesity.
Excessive salt intake causes increased blood pressure which is considered the leading risk for premature death. One major challenge when evaluating associations between daily salt intake and markers of non-communicable diseases is that a high daily salt intake correlates with obesity, which is also a well described risk factor for poor cardiometabolic outcome. The aim of this study was to evaluate the relationship of estimated daily salt intake with blood pressure and blood lipids and to investigate the effect of taking different measures of obesity into account. We included 3294 men and women aged 18-69 years from a general population based study in Copenhagen, Denmark. Estimated 24-hour sodium excretion was calculated by measurements of creatinine and sodium concentration in spot urine in combination with information of sex, age, height and weight. The relations of estimated 24-hour sodium excretion with blood pressure and blood lipids were evaluated by linear regression models. The daily mean estimated intake of salt was 10.80 g and 7.52 g among men and women, respectively. Daily salt intake was significantly associated with blood pressure (β-estimates 1.18 mm Hg/g salt (systolic) and 0.74 mm Hg/g salt (diastolic), p < 0.0001) - however this association was markedly affected by adjustment for obesity (β-estimates around 0.60 mm Hg/g salt (systolic) and around 0.25 mm Hg/g salt (diastolic), p < 0.05). Also associations between daily salt intake and blood lipids were highly affected by adjustment for obesity. Associations of estimated daily salt intake with blood pressure and blood lipids were highly affected by adjustment for obesity.


Incidence, Severity, and Outcomes of Acute Kidney Injury in Octogenarians following Heart Valve Replacement Surgery.
Background. The study investigates the occurrence, severity, and outcomes of acute kidney injury (AKI) in octogenarians following heart valve surgery. Methods. All patients, age >80 years, not on dialysis and without kidney transplant, undergoing heart valve replacement at Mayo Clinic, Rochester, in the years 2002-2003 were enrolled. AKI was diagnosed based on AKIN criteria. Results. 209 octogenarians (88.0% aortic valve, 6.2% mitral valve, 1.0% tricuspid valve, and 4.8% multivalve) with (58.4%) and without CABG were studied. 34 (16.3%) had preexisting CKD. After surgery, 98 (46.8%) developed AKI. 76.5% of the AKI were in Stage 1, 9.2% in Stage 2, and 14.3% in Stage 3. 76.5% CKD patients developed AKI. Length of hospital stay was longer for AKI patients. More AKI patients were discharged to care facilities. Patient survival at 30 days and 1 year for AKI versus non-AKI was 88.8 versus 98.7%, p = 0.003, and 76.5 versus 88.3%, p = 0.025, respectively. With follow-up of 3.94 ± 0.28 years, Kaplan-Meier analysis showed a reduced survival for AKI octogenarians. Preexisting CKD and large volume intraoperative fluid administration were independent AKI predictors. Conclusions. Nearly half of the octogenarians developed AKI after valve replacement surgery. AKI was associated with significant functional impairment and reduced survival.


A comparison of methods for quantifying training load: relationships between modelled and actual training responses.
To assess the validity of methods for quantifying training load, fitness and fatigue in endurance athletes using a mathematical model. Seven trained runners (VO2max: 51.7 ± 4.5 mL kg(-1) min(-1), age: 38.6 ± 9.4 years, mean ± SD) completed 15 weeks of endurance running training. Training sessions were assessed using a heart rate (HR), running pace and rating of perceived exertion (RPE). Training dose was calculated using the session-RPE method, Banisters TRIMP and the running training stress score (rTSS). Weekly running performance (1,500-m time trial), fitness (submaximal HR, resting HR) and fatigue [profile of mood states, heart rate variability (HRV)] were measured. A mathematical model was applied to the training data from each runner to provide individual estimates of performance, fitness and fatigue. Correlations assessed the relationships between the modelled and actual weekly performance, fitness and fatigue measures within each runner. Training resulted in 5.4 ± 2.6 % improvement in 1,500-m performance. Modelled performance was correlated with actual performance in each subject, with relationships being r = 0.70 ± 0.11, 0.60 ± 0.10 and 0.65 ± 0.13 for the rTSS, session-RPE and TRIMP input methods, respectively. There were moderate correlations between modelled and actual fitness (submaximal HR) for the session-RPE (-0.43 ± 0.37) and TRIMP (-0.48 ± 0.39) methods and moderate-to-large correlations between modelled and actual fatigue measured through HRV indices for both session-RPE (-0.48 ± 0.39) and TRIMP (-0.59 ± 0.31) methods. These findings showed that each of the training load methods investigated are appropriate for quantifying endurance training dose and that submaximal HR and HRV may be useful for monitoring fitness and fatigue, respectively.


Oxalate secretion in the rat proximal tubule.
Simultaneous capillary and luminal microperfusion studies in the proximal convoluted tubule of the rat were performed to examine the transepithelial secretory flux of [14C]oxalate. Increases in the concentration of oxalate in the capillary solution from 0.096 to 4.3 mM resulted in progressively higher rates of oxalate secretion into the lumen. Further increases in the capillary concentration of oxalate indicated a tendency toward a plateau. The inclusion of para-chloromercuribenzoate, sodium cyanide, indanyloxyacetic acid, furosemide, or para-aminohippurate in the capillary solution significantly lowered the secretory flux of oxalate. the addition of probenecid in a concentration of 10(-4) M inhibited oxalate secretion when the oxalate concentration in the capillary solution ranged between 1.1 and 4.3 mM, but did not affect oxalate secretion at higher capillary concentrations of oxalate. These results indicate that oxalate secretion in the rat proximal tubule is an active carrier-mediated process. When considered in conjunction with prior studies, the present investigations suggest the possibility that more than one oxalate secretory system exists in the rat proximal tubule.


Understanding socio-economic determinants of childhood mortality: a retrospective analysis in Uganda.
Teso sub-region of Eastern Uganda had superior indices of childhood survival during the period 1959 to 1969 compared to the national average. We analysed the reasons that could explain this situation with a view of suggesting strategies for reducing childhood mortality. We compared the childhood mortalities and their average annual reduction rate (AARR) of Teso sub-region with those of Uganda for the period 1959 to 1969. We also compared indicators of social economic well being (such as livestock per capita and per capita intake of protein/energy). In addition data was compared on other important determinants of child survival such as level of education and rate of urbanisation. In 1969 the infant mortality rate (IMR) for Teso was 94 per 1000 live births compared to the 120 for Uganda. Between 1959 and 1969 the AARR for IMR for Teso was 4.57% compared to 3% for Uganda. It was interesting that the AARR for Teso was higher than that that of 4.4.% required to achieve millennium development goal number four (MDG4). The rate of urbanisation and the level of education were higher in Uganda compared to Teso during the same period. Teso had a per capita ownership of cattle of 1.12 compared to Uganda's 0.44. Teso sub region had about 3 times the amount of protein and about 2 times the amount of calories compared to Uganda. We surmise that higher ownership of cattle and growing of high protein and energy foods might have been responsible for better childhood survival in Teso compared to Uganda.


HIV/AIDS and Postnatal Depression at the University Teaching Hospital, Lusaka, Zambia.
OBJECTIVE: To study the contribution of HIV/AIDS to the problem of postnatal depression among women receiving postnatal care at University Teaching Hospital (UTH), Lusaka, Zambia. BACKGROUND: Postnatal depression (PND), a major depressive episode during the puerperium, affects between 10% and 22% of adult women before the infant's first birthday. HIV seropositivity has been associated with increased risk of mental disease, but its influence on postnatal depression has not been fully explored. METHODS: This was a cross-sectional study, involving 229 mothers receiving postnatal care at UTH. The presence of postnatal depression and mean scores on the Edinburgh Postnatal Depression Scale (EPDS) were assessed, along with the patients' HIV status and other demographic and clinical characteristics. RESULTS: 146 of 229 patients (64%) had depressive symptoms as measured by an EPDS score ≥ 8. Sixty-four women (28%) had severe PND, defined as an EPDS score ≥ 13. There were 46 HIV positive women (20.1%). HIV status was not associated with PND (adjusted OR 1.22, 95% CI 0.50-2.96) or severe PND (adjusted OR 1.77, 95% CI 0.68-4.61). Mixed mode of infant feeding and parity of 4-5 were independently associated with PND. CONCLUSIONS: Depression is a real health problem among mothers attending postnatal care at UTH. HIV status was not independently associated with increased risk of postnatal depression. Keywords: postnatal depression, puerperium, Edinburgh Postnatal Depression Scale, prevalence of HIV/AIDS.


Impact of occupational characteristics on return to work for employed patients after elective lumbar spine surgery.
Low back pain has an immense impact on the US economy. A significant number of patients undergo surgical management in order to regain meaningful functionality in daily life and in the workplace. Return to work (RTW) is a key metric in surgical outcomes, as it has profound implications for both individual patients and the economy at large. In this study, we investigated the factors associated with RTW in patients who achieved otherwise favorable outcomes after lumbar spine surgery. This study retrospectively analyzes prospectively collected data from the lumbar module of national spine registry, the Quality Outcomes Database (QOD). The lumbar module of QOD includes patients undergoing lumbar surgery for primary stenosis, disc herniation, spondylolisthesis (Grade I) and symptomatic mechanical disc collapse or revision surgery for recurrent same-level disc herniation, pseudarthrosis, and adjacent segment disease. Exclusion criteria included age under 18 years and diagnoses of infection, tumor, or trauma as the cause of lumbar-related pain. The outcome of interest for this study was the return to work 12-month after surgery. The lumbar module of QOD was queried for patients who were employed at the time of surgery. Good outcomes were defined as patients who had no adverse events (readmissions/complications), had achieved 30% improvement in Oswestry disability index (ODI) and were satisfied (NASS satisfaction) at 3-month post-surgery. Distinct multivariable logistic regression models were fitted with 12-month RTW as outcome for a. overall population and b. the patients with good outcomes. The variables included in the models were age, gender, race, insurance type, education level, occupation type, currently working/on-leave status, workers' compensation, ambulatory status, smoking status, anxiety, depression, symptom duration, number of spinal levels, diabetes, motor deficit, and preoperative back-pain, leg-pain and ODI score. Of the total 12,435 patients, 10,604 (85.3%) had successful RTW at 1-year postsurgery. Among patients who achieved good surgical outcomes, 605 (7%) failed to RTW. For both the overall and subgroup analysis, older patients had lower odds of RTW. Females had lower odds of RTW compared with males and patients with higher back pain and baseline ODI had lower odds of RTW. Patients with longer duration of symptoms, more physically demanding occupations, worker's compensation claim and those who had short-term disability leave at the time of surgery had lower odds of RTW independent of their good surgical outcomes. This study identifies certain risk factors for failure to RTW independent of surgical outcomes. Most of these risk factors are occupational; hence, involving the patient's employer in treatment process and setting realistic expectations may help improve the patients' work-related functionality.


Application of Raman Spectroscopy for Sorption Analysis of Functionalized Porous Materials.
Functionalized porous materials could play a key role in improving the efficiency of gas separation processes as required by applications such as carbon capture and storage (CCS) and across the hydrogen value chain. Due to the large number of different functionalizations, new experimental approaches are needed to determine if an adsorbent is suitable for a specific separation task. Here, it is shown for the first time that Raman spectroscopy is an efficient tool to characterize the adsorption capacity and selectivity of translucent functionalized porous materials at high pressures, whereby translucence is the precondition to study mass transport inside of a material. As a proof of function, the performance of three silica ionogels to separate an equimolar (hydrogen + carbon dioxide) gas mixture is determined by both accurate gravimetric sorption measurements and Raman spectroscopy, with the observed consistency establishing the latter as a novel measurement technique for the determination of adsorption capacity. These results encourage the use of the spectroscopic approach as a rapid screening method for translucent porous materials, particularly since only very small amounts of sample are required.


m6A modification negatively regulates translation by switching mRNA from polysome to P-body via IGF2BP3.
In the cytoplasm, mRNAs are dynamically partitioned into translating and non-translating pools, but the mechanism for this regulation has largely remained elusive. Here, we report that m6A regulates mRNA partitioning between polysome and P-body where a pool of non-translating mRNAs resides. By quantifying the m6A level of polysomal and cytoplasmic mRNAs with m6A-LAIC-seq and m6A-LC-MS/MS in HeLa cells, we observed that polysome-associated mRNAs are hypo-m6A-methylated, whereas those enriched in P-body are hyper-m6A-methylated. Downregulation of the m6A writer METTL14 enhances translation by switching originally hyper-m6A-modified mRNAs from P-body to polysome. Conversely, by proteomic analysis, we identify a specific m6A reader IGF2BP3 enriched in P-body, and via knockdown and molecular tethering assays, we demonstrate that IGF2BP3 is both necessary and sufficient to switch target mRNAs from polysome to P-body. These findings suggest a model for the dynamic regulation of mRNA partitioning between the translating and non-translating pools in an m6A-dependent manner.


Successful Treatment of Refractory Seizures With Rufinamide in Children With Schizencephaly: Report of 3 Cases.
Schizencephaly is an uncommon malformation of cortical development. Patients with schizencephaly present with a broad range of severe neurologic symptoms including pharmacoresistant epilepsy. Rufinamide is a new antiepileptic drug approved for use as adjunctive therapy of seizures associated with Lennox-Gastaut syndrome and it is also effective for refractory partial seizures. We report 3 cases of pediatric patients aged 7.2, 8.1, and 10.1 years, respectively, with intractable epilepsy associated with bilateral open-lip schizencephaly and septo-optic dysplasia. The follow-up ranged from 3.8 to 4.1 years. In our patients, the introduction of rufinamide as adjunctive drug led to a dramatic decline in the number of seizures and an improvement in EEG epileptic activity without side effects. Rufinamide seems to be efficacious and safe in patients with epileptic encephalopathies associated with pharmacoresistant epilepsy; further and larger clinical reports and controlled studies could confirm the usefulness of this anticonvulsant drug.


Identification of mecA-related oxacillin resistance in staphylococci by the E test and the broth microdilution method.
A set of 165 strains of different staphylococcal species, 67 Staphylococcus aureus, 71 novobiocin-sensitive coagulase-negative staphylococci (CNS) and 27 novobiocin-resistant CNS was used. The oxacillin and methicillin MICs were recorded after 24 and 42 h of incubation at 35 degrees C and at 30 degrees C. Significantly higher MICs were recorded at 30 degrees C compared with 35 degrees C. While a poor discrimination between mecA-positive and mecA-negative strains was obtained with methicillin, the oxacillin MICs enabled identification of resistant strains under certain conditions. The distribution of MICs differed between the three groups of species. Separation of uninduced mecA-positive (> or = 4.0 mg oxacillin/L) and mecA-negative (< or = 2.0 mg oxacillin/L) strains of S. aureus was only achieved with the E test and after 42 h of incubation. Oxacillin-induction yielded higher MICs for mecA-positive strains of S. aureus, and a separation from mecA-negative strains was achieved with the E test after 24 h and with the broth microdilution method after 42 h. Separation of mecA-positive and mecA-negative strains of novobiocin-sensitive CNS required agar supplemented with 5% blood, incubation of MIC trays and E test for 42 h, and species-specific oxacillin MIC breakpoints (S < or = 0.5 mg/L and R > or = 1.0 mg/L). The mecA-positive and mecA-negative strains of novobiocin-resistant CNS were clearly separated after 24 h of incubation by either method.


Global transcriptional analysis of Escherichia coli expressing IrrE, a regulator from Deinococcus radiodurans, in response to NaCl shock.
Improving the microbial tolerance to stresses is very important for bioprocesses. Our previous study showed that IrrE, a global regulator from the extremely radioresistant bacterium Deinococcus radiodurans, dramatically enhanced the multi-stress tolerance of Escherichia coli when expressed exogenously. However, the function of IrrE is still unclear. In this study, we used whole-genome microarray assays to profile the global gene expression of the IrrE-expressing E. coli strain MGE and the control strain MGT with or without salt shock. The analysis showed that IrrE expression led to many differentially expressed genes in E. coli, which were responsible for the transport and metabolism of trehalose and glycerol, nucleotide biosynthesis, carbon source utilization, amino acid utilization, and acid resistance, including many RpoS-dependent genes, e.g., the trehalose biosynthesis genes otsAB, the acid-resistance genes gadABC and uspB, the osmotic and oxidative stress response genes katE (response to DNA damage stimulus and stress) and osmBC (response to stress), and gadWX (which controls the transcription of pH-inducible genes). The intracellular content of trehalose and glycerol increased significantly in the IrrE-expressing strain after NaCl treatment for 0 and 60 min as determined by HPLC. These results indicated the possibility that IrrE regulates the global regulator RpoS. Interestingly, we found that although IrrE did not affect the level of the rpoS transcript, it enhanced the accumulation of the RpoS protein by increasing the expression of the antiadaptors, AppY, IraM and IraD, which inhibit RpoS degradation, suggesting that the accumulation of RpoS due to IrrE regulation is an important way to improve tolerance to salt and other stresses in E. coli.


Antioxidant and antibacterial activities of Pelargonium asperum and Ormenis mixta essential oils and their synergistic antibacterial effect.
In this work, the chemical composition, the antioxidant, and the antibacterial activities of two Moroccan essential oils less studied, extracted from Pelargonium asperum and Ormenis mixta, were investigated. According to the gas chromatography coupled to mass spectrometry analysis, citronellol (25.07%), citronellyl ester (10.52%), geraniol (10.46%), and buthyl anthranilate (5.93%) were found to be the major components of P. asperum, while O. mixta was mainly composed of D-germacrene (11.46%), 1,8-cineole (10.28%), and cis-methyl isoeugenol (9.04%). Moreover, O. mixta essential oil exhibited an important antioxidant activity being significantly higher than that exhibited by P. asperum oil (P < 0.001). As regards the antimicrobial activity of both essential oils, the zones of growth inhibition and the minimum inhibitory concentration values showed that P. asperum essential oil was more active than that of O. mixta. Thereafter, the impact of the binary combination of essential oils on their antimicrobial effect was investigated against Staphylococcus aureus using the fractional inhibitory concentration index calculation. The results showed a promising synergistic antibacterial interaction between essential oils studied.


Estimation of elliptical basis function parameters by the EM algorithm with application to speaker verification.
This paper proposes to incorporate full covariance matrices into the radial basis function (RBF) networks and to use the expectation-maximization (EM) algorithm to estimate the basis function parameters. The resulting networks, referred to as elliptical basis function (EBF) networks, are evaluated through a series of text-independent speaker verification experiments involving 258 speakers from a phonetically balanced, continuous speech corpus (TIMIT).We propose a verification procedure using RBF and EBF networks as speaker models and show that the networks are readily applicable to verifying speakers using LP-derived cepstral coefficients as features. Experimental results show that small EBF networks with basis function parameters estimated by the EM algorithm outperform the large RBF networks trained in the conventional approach. The results also show that the equal error rate achieved by the EBF networks is about two-third of that achieved by the vetor quantization (VQ)-based speaker models.


Is EEG a useful test in adult psychiatry?
We present a brief overview of the use of EEG in psychiatry, with particular emphasis on differential diagnosis examination in case of acute psychiatric conditions. The article is based on a literature search in PubMed and the authors' own collections of articles and personal experience. Onset of epilepsy, encephalitis or other cerebral diseases may be accompanied by psychiatric or cognitive symptoms. Slow EEG activity may be an unspecific sign of cerebral disease. Psychiatric patients are also at an increased risk of epilepsy. In case of seizure symptoms such as convulsions or conditions with rapid changes in affective states, epileptiform activity during EEG is a specific sign of epileptic aetiology or comorbidity. Quantitative frequency analysis (QEEG) is useful for research purposes and in exceptional cases also in a clinical context. No QEEG method has as yet become accepted as providing reliable, independent markers for psychiatric disease or treatment response. EEG should be undertaken in case of newly occurring psychoses and for conditions with a fluctuating or progradiating loss of cognitive function. Adult psychiatric patients with seizure symptoms or rapid changes in affective states should also be referred to EEG.


Spontaneous regression of cancer and the importance of finding its cause.
A few years ago Everson and I assembled all the examples of spontaneous regression in the world medical literature from 1900 to 1960 and added numerous cases from expriences of our friends. Our figure was 176. We excluded squamous cell carcinoma of the skin, leukemia, Hodgkin's disease, and a large number of cases that did not fulfill the prerequisites of confirmed diagnosis and no significant treatment. The four most common examples of regression were carcinoma of the kidney (31), neuroblastoma (29), malignant melanoma (19), and choriocarcinoma (19); these constituted more than half the group. We did not require that the regression be permanent because it appeared that the explanation of temporary regression would be just as important as the cause of permanent regression. There was no proven specific cause of the regression, but the following mechanisms had a possible relationship: immunologic action, elimination of carcinogens, trauma (altering the antigen-antibody relationship), hormones, irradiation, infection and/or fever, and drugs or chemicals. The most applicable of these is elimination of the carcinogen. Immunologic reactions seem to offer the best explanation, and the potential of humoral immunity is more impressive than that of cellular immunity.


Nanoscale imaging of InN segregation and polymorphism in single vertically aligned InGaN/GaN multi quantum well nanorods by tip-enhanced Raman scattering.
Vertically aligned GaN nanorod arrays with nonpolar InGaN/GaN multi quantum wells (MQW) were grown by MOVPE on c-plane GaN-on-sapphire templates. The chemical and structural properties of single nanorods are optically investigated with a spatial resolution beyond the diffraction limit using tip-enhanced Raman spectroscopy (TERS). This enables the local mapping of variations in the chemical composition, charge distribution, and strain in the MQW region of the nanorods. Nanoscale fluctuations of the In content in the InGaN layer of a few percent can be identified and visualized with a lateral resolution below 35 nm. We obtain evidence for the presence of indium clustering and the formation of cubic inclusions in the wurtzite matrix near the QW layers. These results are directly confirmed by high-resolution TEM images, revealing the presence of stacking faults and different polymorphs close to the surface near the MQW region. The combination of TERS and HRTEM demonstrates the potential of this nanoscale near-field imaging technique, establishing TERS as a very potent, comprehensive, and nondestructive tool for the characterization and optimization of technologically relevant semiconductor nanostructures.


Effect of lubricants on friction in laboratory tests of a total disc replacement device.
Some designs of total disc replacement devices have articulating bearing surfaces, and these devices are tested in vitro with a lubricant of diluted calf serum. It is believed that the lubricant found in total disc replacement devices in vivo is interstitial fluid that may have properties between that in Ringer's solution and diluted calf serum. To investigate the effect of lubricants, a set of friction tests were performed on a generic model of a metal against metal ball-and-socket total disc replacement device. Two devices were tested: one with a ball radius of 10 mm and other with a ball radius of 16 mm; each device had a radial clearance of 0.015 mm. A spine simulator was used to measure frictional torque for each device in axial rotation, flexion-extension and lateral bending at frequencies of 0.25-2 Hz, under 1200 N axial load. Each device was tested with two different lubricants: a solution of new born calf serum diluted with deionised water and Ringer's solution. The results showed that the frictional torque generated between the bearing surfaces was significantly higher in Ringer's solution than in diluted calf serum. The use of Ringer's solution as a lubricant provides a stringent test condition to detect possible problems. Diluted calf serum is more likely to provide an environment closer to that in vivo. However, the precise properties of the fluid lubricating a total disc replacement device are not known; hence, tests using diluted calf serum may not necessarily give the same results as those obtained in vivo.


Recent developments in anticancer kinase inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold.
Pyrazolo[3,4-d]pyrimidines have become of significant interest for the medicinal chemistry community as a privileged scaffold for the development of kinase inhibitors to treat a range of diseases, including cancer. This fused nitrogen-containing heterocycle is an isostere of the adenine ring of ATP, allowing the molecules to mimic hinge region binding interactions in kinase active sites. Similarities in kinase ATP sites can be exploited to direct the activity and selectivity of pyrazolo[3,4-d]pyrimidines to multiple oncogenic targets through focussed chemical modification. As a result, pharma and academic efforts have succeeded in progressing several pyrazolo[3,4-d]pyrimidines to clinical trials, including the BTK inhibitor ibrutinib, which has been approved for the treatment of several B-cell cancers. In this review, we examine the pyrazolo[3,4-d]pyrimidines currently in clinical trials for oncology patients, as well as those published in the literature during the last 5 years for different anticancer indications.


[The genetic value of embryo transfer in South Africa (author's transl)].
The different applications of embryo transfer from the animal improvement, scientific and commercial point of view are outlined. The most important application in South Africa is the production of the next generation's dairy A.I. bulls out of elite cows after superovulation, inseminations with the best available semen and embryo transfer to many foster mothers. The specific difficulties of running breeding programmes with small active breeding populations are discussed, and it is suggested that elite cows should be brought to special farms or government stations during the period of superovulation and transfer. In this way the disadvantage of small breeding populations could to a certain extent be overcome by embryo transfer.


Kidney neutral endopeptidase and the hydrolysis of enkephalin by synaptic membranes show similar sensitivity to inhibitors.
Neutral endopeptidase (EC 188.8.131.52) from pig kidney hydrolyses [125I]iodo-insulin B-chain and leucine-enkephalin. Both activities were equally sensitive to inhibition by phosphoramidon [N-(alpha-L-rhamnopyranosyloxyhydroxyphosphinyl)-L-leucyl-L-tryptophan] and thiorphan [N-(DL-2-benzyl-3-mercaptopropionyl)glycine]. Thermolysin hydrolysis of insulin B-chain was also sensitive to both inhibitors. The hydrolysis of the Gly3-Phe4 bond of Leu-enkephalin by synaptic membranes prepared from pig brain was partially inhibited by phosphoramidon and thiorphan. Synaptic membranes appear to contain another endopeptidase activity that is insensitive to these reagents. These observations suggest that enzymes similar to the kidney endopeptidase may play a general role in neuropeptide metabolism.


Multivalley engineering in semiconductor microcavities.
We consider exciton-photon coupling in semiconductor microcavities in which separate periodic potentials have been embedded for excitons and photons. We show theoretically that this system supports degenerate ground-states appearing at non-zero inplane momenta, corresponding to multiple valleys in reciprocal space, which are further separated in polarization corresponding to a polarization-valley coupling in the system. Aside forming a basis for valleytronics, the multivalley dispersion is predicted to allow for spontaneous momentum symmetry breaking and two-mode squeezing under non-resonant and resonant excitation, respectively.


High incidence of pneumonia in elderly patients with basal ganglia infarction.
Pneumonia is a major cause of death in patients with cerebral infarction. We assessed morbidity associated with pneumonia in 276 patients 65 years of age or older who were admitted to a long-term care facility. Furthermore, we studied the swallowing reflex during the day and at night and monitored the occurrence of silent aspiration during sleep. To examine the possible relationship between the location of cerebral hemispheric infarctions and the incidence of pneumonia and to evaluate the role of silent aspiration in the development of pneumonia. The incidence of pneumonia was analyzed in 4 groups of patients who were assigned to a group on the basis of the following computed tomographic findings: no infarct (group A); 1 or more unilateral basal ganglia infarcts (group B); bilateral basal ganglia infarcts (group C); and 1 or more cerebral hemispheric infarcts outside the basal ganglia (group D). Criteria for diagnosis of pneumonia were (1) a new pulmonary infiltrate seen on a chest radiograph and (2) 1 or more of the following features: cough, temperature greater than 37.8 degrees C, or subjective dyspnea. Before the study, the patients with stroke were followed up for more than 1 year after their ictus and were monitored to determine if they sustained affecting cerebral hemispheric structures. The average duration of observation for incidence of pneumonia was 22 months. To study the swallowing reflex and to monitor for the occurrence of silent aspiration during sleep, 15 of the patients who were confined to bed or chair were randomly selected from each of groups A through C. The swallowing reflex was examined at both 1 PM and 1 AM and was evaluated according to latency of response, which was timed from the injection of 1 mL of distilled water into the pharynx through a nasal catheter to the onset of swallowing. The incidence of silent aspiration during sleep was examined using indium-111 chloride as a radioactive tracer attached to the teeth, and scanning of the thorax was performed the next morning. The incidence of pneumonia was 2.12 times higher in the patients of group B (27.4%; P < .01) and 3.64 times higher in the patients of group C (47.0%; P < .001) than in the patients of group A (12.9%). The latency of response was longer in the patients of groups B (P < .05) and C (P < .001) than in those of group A at 1 AM. The percentage of positive scans was also higher in the patients of groups B (P < .01) and C (P < .001) than in those of group A. Basal ganglia strokes might predispose these patients to develop pneumonia owing to frequent aspiration during sleep.


Technical Note: A method for quality assurance of landmark sets for use in evaluation of deformable image registration accuracy of lung parenchyma.
To develop a quality control method to improve the accuracy of corresponding landmark sets used for deformable image registration (DIR) evaluation in the lung parenchyma. An iterative workflow was developed as a method for quality assurance of landmark sets. Starting with the initial landmark set for a given image pair, a landmark-based deformation was applied to one of the images. A difference image and a color overlay were generated using the deformed image and the other image of the pair. Inspection of these generated images at locations of landmarks allowed for the identification of misplaced landmarks. The observer responsible for creating the initial landmark set was tasked with review and revision of points flagged by the quality assurance procedure. Using the updated landmark sets, the process was repeated until all points were acceptable to the reviewer. Eighteen landmark sets, containing a mean (SD) of 170 (31) landmarks, were created using CT images from non-small cell lung cancer patients exhibiting large geometric changes and atelectasis resolution, making landmark specification challenging. Following the quality assurance procedure, the final landmark sets contained a mean (SD) of 165 (25) landmarks, as points too difficult to match were removed and points were added to regions deficient in landmarks. For landmark sets in which changes were made, maximum and mean differences in landmark positions before and after quality assurance ranged between 8.7-81.5 mm and 0.3-9.6 mm, respectively. An effective method for improving the accuracy of landmark correspondence was presented. This quality assurance approach enables more accurate evaluation of DIR for lung parenchyma in clinical image pairs in the absence of a ground truth deformation and may be applicable to other feature-rich anatomical sites.


Cholestatic jaundice: an immune response to prajmalium bitartrate.
Cholestatic jaundice associated with chills, pruritus and blood eosinophilia developed in a patient who received prajmalium bitartrate therapy for ventricular arrhythmia following acute myocardial infarction. Discontinuation of the drug resulted in a spontaneous improvement in the clinical and biochemical findings. Challenge by prajmalium bitartrate caused rapid reappearance of the clinical and biochemical features. In immunological studies, deposits of IgG and IgA were detected at the bile canaliculi by fluorescent staining, and the patient's lymphocytes produced macrophage migration inhibition after in vitro incubation with prajmalium bitartrate. Thus, laboratory results support the assumption of an allergic mechanism.


When loneliness dimensions drift apart: Emotional, social and physical loneliness during the COVID-19 lockdown and its associations with age, personality, stress and well-being.
Previous research differentiated between emotional loneliness (perceived lack of emotional connection with others) and social loneliness (perceived lack of a broader social network). We argue that physical loneliness (perceived lack of physical contact) constitutes a third dimension of loneliness that is particularly relevant in times of physical distancing. We conducted a longitudinal experience sampling study (N = 578) during the first 8 weeks of the COVID-19 lockdown in Germany to test this claim. The results indicate that loneliness has a three-dimensional structure encompassing emotional, social and physical loneliness. Each loneliness dimension explained a unique variance in perceived stress and psychological well-being. However, the three loneliness dimensions differed in their prevalence during the contact restrictions and their associations with age and personality. Physical loneliness was higher during the contact restrictions whereas emotional and social loneliness remained on a normal level. Age was positively associated with social loneliness but negatively associated with physical loneliness. Extraversion was negatively associated with emotional and social loneliness but positively associated with physical loneliness. These findings expand loneliness models, enhance loneliness assessment and improve the prediction of vulnerability to loneliness.


The immunobiology and clinical features of type 1 autoimmune polyglandular syndrome (APS-1).
Autoimmune Polyglandular Syndrome type 1 (APS-1) is a subtype of the autoimmune polyendocrine syndrome characterized by the simultaneous or sequential dysfunction of multiple endocrine or non-endocrine glands. A clinical diagnosis of APS-1 is typically based on the presence of at least two of three following criteria: chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. The first identified causative mutated gene for APS-1 is autoimmune regulator (AIRE) encoding a critical transcription factor, which is primarily expressed in the medullary thymic epithelial cells (mTECs) for generating central immune tolerance. A wide range of chronic, debilitating complications, with no obvious correlation with genetics, makes a diagnosis of APS-1 challenging early in the disease course. Managing APS-1 is difficult due to its complexity, especially the intricate relationships within manifestations and genetic mutations. The past decades have witnessed dramatic progress in elucidating the function of AIRE and conducting large-scale cohort studies in APS-1. However, no clear evidence-based guidelines have been established in APS-1. In this review, we provide a detailed critical overview of the study history, epidemiology, clinical features, and related mechanisms of autoimmunity in APS-1, as well as currently available therapies for this autoimmune disorder.


Electromagnetic fields applied to the reduction of abdominal obesity.
According to various researches, abdominal obesity increases the risks of cancers or cardio-vascular diseases. To evaluate the reduction of waistline and the evolution of biological parameters on patients after 12 sessions of a new medical device called REDUSTIM(®) associating alternate low frequency electromagnetic fields and controlled micropressure. Two studies were made: a double-blind randomized study performed on 28 patients with a waistline > 88 cm/35 inches for women and > 102 cm/40 inches for men for a period of 6 weeks and a functional analysis on DNA chips performed on 11 patients showing proven overweight. Following our studies a statistically significant reduction of waistline of more than 6 cm after 12 sessions has been observed, and the biological assessments performed before and after the treatments showed both a highly significant reduction of transaminases level and the device mechanism on the stimulation of insensitive muscle contractions. Facing an alarming increase in overweight and obesity and considering the current therapeutic gear offering various results, it seems interesting to propose an efficient technique for the reduction of abdominal obesity. The clinical study demonstrated the safety and efficiency of the device for the reduction of abdominal obesity. Treatment showed itself efficient with patients who were not committed to any weight loss program.


Effect of sociality and season on gray wolf (Canis lupus) foraging behavior: implications for estimating summer kill rate.
Understanding how kill rates vary among seasons is required to understand predation by vertebrate species living in temperate climates. Unfortunately, kill rates are only rarely estimated during summer. For several wolf packs in Yellowstone National Park, we used pairs of collared wolves living in the same pack and the double-count method to estimate the probability of attendance (PA) for an individual wolf at a carcass. PA quantifies an important aspect of social foraging behavior (i.e., the cohesiveness of foraging). We used PA to estimate summer kill rates for packs containing GPS-collared wolves between 2004 and 2009. Estimated rates of daily prey acquisition (edible biomass per wolf) decreased from 8.4±0.9 kg (mean ± SE) in May to 4.1±0.4 kg in July. Failure to account for PA would have resulted in underestimating kill rate by 32%. PA was 0.72±0.05 for large ungulate prey and 0.46±0.04 for small ungulate prey. To assess seasonal differences in social foraging behavior, we also evaluated PA during winter for VHF-collared wolves between 1997 and 2009. During winter, PA was 0.95±0.01. PA was not influenced by prey size but was influenced by wolf age and pack size. Our results demonstrate that seasonal patterns in the foraging behavior of social carnivores have important implications for understanding their social behavior and estimating kill rates. Synthesizing our findings with previous insights suggests that there is important seasonal variation in how and why social carnivores live in groups. Our findings are also important for applications of GPS collars to estimate kill rates. Specifically, because the factors affecting the PA of social carnivores likely differ between seasons, kill rates estimated through GPS collars should account for seasonal differences in social foraging behavior.


Effect of reproterol either alone or combined with disodium cromoglycate on airway responsiveness to methacholine.
Regular use of inhaled beta2-agonists might lead to tolerance as reflected in a loss of bronchoprotection. In vitro-data suggest that this might be prevented by disodium cromoglycate (DSCG). Therefore, we studied the effect of the beta2-agonist reproterol in combination with DSCG. In a cross-over design, 19 subjects with airway hyperresponsiveness inhaled either placebo, 1mg reproterol, 2 mg DSCG, or 1mg reproterol plus 2 mg DSCG 4x daily over 2 weeks. Treatment periods were separated by > or = 7 days. Before and at the end of periods, lung function and methacholine responsiveness were determined in the morning, and 6h later the bronchodilator effect and the protection against methacholine-induced bronchoconstriction. Reproterol or DSCG or their combination did not exert detrimental effects on lung function, airway responsiveness, or bronchodilator capacity. However, bronchoprotection was significantly reduced (p < 0.05) after treatment with placebo, reproterol or reproterol plus DSCG, the respective changes being 0.59, 0.96 and 1.37 doubling concentrations. All changes were small as compared to intraindividual variability. In this model all treatments except with DSCG caused a significant but small loss of protection against methacholine-induced bronchoconstriction. Thus, tolerance was not prevented by 2 weeks of additional treatment with DSCG, in contrast to in vitro findings.


Chromosome identification and nomenclature of Sorghum bicolor.
Linkage group identities and homologies were determined for metaphase chromosomes of Sorghum bicolor (2n = 20) by FISH of landed BACs. Relative lengths of chromosomes in FISH-karyotyped metaphase spreads of the elite inbred BTx623 were used to estimate the molecular size of each chromosome and to establish a size-based nomenclature for sorghum chromosomes (SBI-01-SBI-10) and linkage groups (LG-01 to LG-10). Lengths of arms were determined to orient linkage groups relative to a standard karyotypic layout (short arms at top). The size-based nomenclature for BTx623 represents a reasonable choice as the standard for a unified chromosome nomenclature for use by the sorghum research community.


Assessing the potential of wild foods to reduce the cost of a nutritionally adequate diet: an example from eastern Baringo District, Kenya.
Wild foods and their actual and potential contributions to nutrition security have rarely been studied or considered in nutrition and conservation programs. To study the role of wild food biodiversity in achieving a cost reduction of a nutritionally adequate diet for women and young children in Kenya using linear programming. An ethnobiological inventory of available food biodiversity was carried out by means of focus group discussions, and five wild foods were selected for further modeling. A market survey assessed available food prices by season. Diets were modeled to minimize cost and maximize nutrient adequacy using the Cost of Diet linear programming tool. Modeling was done without and with wild foods. The modeled diets without wild species were deficient in iron for all age groups during the dry season, deficient in vitamin B6 and calcium for infants aged 6 to 8 months during the dry season, and deficient in iron and zinc for infants aged 6 to 8 months over the whole year. Adding wild foods, especially Berchemia discolor, to the modeled diets resulted in a lower-cost diet, while meeting recommended iron intakes for women and children between 12 and 23 months of age. Even after integrating wild foods into the model, targeted approaches are needed to meet micronutrient requirements for infants from 6 to 8 and from 9 to 11 months of age. An application of linear programming to screen available wild foods for meeting recommended nutrient intakes at a minimal cost was illustrated. This type of study helps to objectively assess the potential of biodiversity to contribute to diets and nutrition.


Genomic variation among populations of threatened coral: Acropora cervicornis.
Acropora cervicornis, a threatened, keystone reef-building coral has undergone severe declines (>90 %) throughout the Caribbean. These declines could reduce genetic variation and thus hamper the species' ability to adapt. Active restoration strategies are a common conservation approach to mitigate species' declines and require genetic data on surviving populations to efficiently respond to declines while maintaining the genetic diversity needed to adapt to changing conditions. To evaluate active restoration strategies for the staghorn coral, the genetic diversity of A. cervicornis within and among populations was assessed in 77 individuals collected from 68 locations along the Florida Reef Tract (FRT) and in the Dominican Republic. Genotyping by Sequencing (GBS) identified 4,764 single nucleotide polymorphisms (SNPs). Pairwise nucleotide differences (π) within a population are large (~37 %) and similar to π across all individuals. This high level of genetic diversity along the FRT is similar to the diversity within a small, isolated reef. Much of the genetic diversity (>90 %) exists within a population, yet GBS analysis shows significant variation along the FRT, including 300 SNPs with significant FST values and significant divergence relative to distance. There are also significant differences in SNP allele frequencies over small spatial scales, exemplified by the large FST values among corals collected within Miami-Dade county. Large standing diversity was found within each population even after recent declines in abundance, including significant, potentially adaptive divergence over short distances. The data here inform conservation and management actions by uncovering population structure and high levels of diversity maintained within coral collections among sites previously shown to have little genetic divergence. More broadly, this approach demonstrates the power of GBS to resolve differences among individuals and identify subtle genetic structure, informing conservation goals with evolutionary implications.


Modulation of adrenergic responses in pressurized resistance arteries by flow.
The effects of perfusion on the reactivity of isolated rat resistance mesenteric arteries (200 micron ID) to electrical stimulation and exogenous norepinephrine (NE) were investigated. Diameter constrictions of these arteries that have an intact endothelium in response to the stimuli were significantly greater (P less than 0.05) in the presence than in the absence of flow. Inhibition of NE uptake and metabolism with cocaine, normetanephrine, and pargyline increased constrictor responses to electrical stimulation and NE in the presence and absence of flow, but responses remained larger in the presence of flow. Endothelial cell removal augmented the NE-induced diameter constrictions, which were not different whether or not flow was present. Perfusion at similar flows but a higher shear stress using a dextran solution led to smaller constrictions than obtained at lower shear stress in response to NE. However, NE-induced constrictions at high and low shear stresses were the same after endothelium removal. These observations suggest that NE and elevated levels of shear stress induce the release of relaxing factors from the endothelium, which attenuates direct NE smooth muscle cell constrictor responses.


Sea urchin maternal and embryonic U1 RNAs are spatially segregated in early embryos.
We have used in situ hybridization and cell fractionation methods to follow the distribution of U1 RNA and immunofluorescence microscopy to follow the distribution of snRNP proteins in oocytes, eggs, and embryos of several sea urchin species. U1 RNA and U1-specific snRNP antigens are concentrated in germinal vesicles of oocytes. Both appear to relocate after oocyte maturation because they are found primarily, if not exclusively, in the cytoplasm of mature unfertilized eggs. This cytoplasmic residence is maintained during early cleavage and U1 RNA is first detectable in nuclei of micromeres at the 16-cell stage. Between morula and gastrula stages the steady-state concentrations of both RNA and antigens gradually increase in nuclei and decrease in cytoplasm. Surprisingly, analysis of the distribution of newly synthesized U1 RNA shows that it does not equilibrate with the maternal pool. Instead new transcripts are confined to nuclei, while cytoplasmic U1 RNAs are of maternal origin. This lack of equilibration and the conversion of maternal U1 RNAs from nuclear species in oocytes to cytoplasmic in embryos suggests that these RNPs (or RNAs) are structurally altered when released to the cytoplasm at oocyte maturation.


MEG-SIM: a web portal for testing MEG analysis methods using realistic simulated and empirical data.
MEG and EEG measure electrophysiological activity in the brain with exquisite temporal resolution. Because of this unique strength relative to noninvasive hemodynamic-based measures (fMRI, PET), the complementary nature of hemodynamic and electrophysiological techniques is becoming more widely recognized (e.g., Human Connectome Project). However, the available analysis methods for solving the inverse problem for MEG and EEG have not been compared and standardized to the extent that they have for fMRI/PET. A number of factors, including the non-uniqueness of the solution to the inverse problem for MEG/EEG, have led to multiple analysis techniques which have not been tested on consistent datasets, making direct comparisons of techniques challenging (or impossible). Since each of the methods is known to have their own set of strengths and weaknesses, it would be beneficial to quantify them. Toward this end, we are announcing the establishment of a website containing an extensive series of realistic simulated data for testing purposes ( http://cobre.mrn.org/megsim/ ). Here, we present: 1) a brief overview of the basic types of inverse procedures; 2) the rationale and description of the testbed created; and 3) cases emphasizing functional connectivity (e.g., oscillatory activity) suitable for a wide assortment of analyses including independent component analysis (ICA), Granger Causality/Directed transfer function, and single-trial analysis.


Biology of disease. Alcoholism and aldehydism: new biomedical concepts.
New results of biomedical research in alcoholism show great interindividual, as well as racial, variability with respect to metabolism of alcohol and its first oxidation product, acetaldehyde. Genetic factors play an important part. The enzymes of alcohol and aldehyde metabolism exhibit a genetically determined heterogeneity (isoenzymes and enzyme polymorphisms). This leads to a large variety of individually different enzyme phenotypes. Thus, the hypothesis is put forward that the individual and racial differences in alcohol metabolism are based on the genetically determined variability of the participating enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Alcohol metabolism and alcohol-induced disturbances of the intermediary metabolism are closely interrelated. Hence, genetic codetermination can also be expected in this regard. As a toxic intermediate of alcohol metabolism, acetaldehyde plays a central role. Three positive ranges of acetaldehyde levels can be defined: (a) the normal range, (b) the "acute aldehyde syndrome" with extremely high levels of acetaldehyde, (c) "chronic aldehydism" with slightly elevated acetaldehyde levels. In Orientals lacking the mitochondrial low Km aldehyde dehydrogenase, acetaldehyde accumulates and produces symptoms of intoxication. This acute aldehyde syndrome is highly aversive and, thus, prevents these individuals from drinking. The effect is similar to the consequences of the inhibition of aldehyde dehydrogenase with disulfiram, a commonly employed drug in the treatment of alcoholics. In alcoholics slightly elevated levels of blood acetaldehyde are observed. There are indications that this chronic aldehydism is not only the consequence of excessive drinking but may reflect a preexisting enzyme pattern that is genetically determined. Therefore, slightly elevated acetaldehyde concentrations could serve as a biologic marker for high risk drinking. Alcohol dehydrogenase is found in many organs and often in specialized cells within a particular tissue. A specific enzyme pattern in these cells could lead to elevated acetaldehyde concentrations, consequently inducing acetaldehyde-related damage. Such organs could represent direct targets even at low blood acetaldehyde levels.


A quantitative model for cyclin-dependent kinase control of the cell cycle: revisited.
The eukaryotic cell division cycle encompasses an ordered series of events. Chromosomal DNA is replicated during S phase of the cell cycle before being distributed to daughter cells in mitosis. Both S phase and mitosis in turn consist of an intricately ordered sequence of molecular events. How cell cycle ordering is achieved, to promote healthy cell proliferation and avert insults on genomic integrity, has been a theme of Paul Nurse's research. To explain a key aspect of cell cycle ordering, sequential S phase and mitosis, Stern & Nurse proposed 'A quantitative model for cdc2 control of S phase and mitosis in fission yeast'. In this model, S phase and mitosis are ordered by their dependence on increasing levels of cyclin-dependent kinase (Cdk) activity. Alternative mechanisms for ordering have been proposed that rely on checkpoint controls or on sequential waves of cyclins with distinct substrate specificities. Here, we review these ideas in the light of experimental evidence that has meanwhile accumulated. Quantitative Cdk control emerges as the basis for cell cycle ordering, fine-tuned by cyclin specificity and checkpoints. We propose a molecular explanation for quantitative Cdk control, based on thresholds imposed by Cdk-counteracting phosphatases, and discuss its implications.


Is it possible to detect a true rotation axis of the temporomandibular joint with common pantographic methods? A fundamental kinematic analysis.
The location of the terminal hinge axis of the temporomandibular joint is still a very wide-spread procedure in dentistry in order to replicate the movement in various articulator devices. Especially pantographic methods are claimed to provide accurate measurements and, additionally, are seen to be able to separate a pure rotation of the joint from a movement with an arbitrary combined shift and rotation. In the latter application, these methods were used in a lot of studies as a reference standard. The aim of this study was to analyze, whether common pantographic methods in general are able to distinguish between a pure rotation and a movement with rotational and translational portions. The mathematical proof of this analysis was done with theoretical kinematic considerations and compared with computer simulations. The results show for the first time that there exist combinations of rotational and translational movements of the temporomandibular joint which cannot be separated from pure rotational movements using actual pantographic methods. Even more, the consequence is a shifted location of the (combined) finite center (axis) of rotation in comparison to the true center (axis) of rotation: in case of a translational portion of only 1 mm, this is a displacement of around ±6 mm and, in case of 2 mm translation, a displacement of ±12 mm. This finding necessitates a critical reinterpretation of former studies using pantographic methods as a reference standard. Further, under some circumstances it may also affect the applicability of articulator concepts and the interpretation of functional signs.


Occupational exposure to antineoplastic drugs in four Italian health care settings.
Exposure assessment of health care workers to antineoplastic drugs (ADs) is still an open issue since new, critical, and emerging factors may put pharmacists who prepare hazardous drugs or nurses who administer anti cancer agents to an increased risk of developing adverse health effects. Overall, eight pharmacies and nine patient areas have been surveyed in this study. Wipe and pad samples were experienced during the surveillance program in four Italian health care settings. Urine samples were collected from workers handling ADs. Cyclophosphamide (CP), ifosfamide (IF), and gemcitabine (GEM) were detected in all the work environments by using a LC-MS/MS method-based capable of analysing all the three drugs simultaneously. In total, 54% of wipe samples were positive for at least one drug and 19% of pad samples were shown to be contaminated by cyclophosphamide. Pharmacies were generally more contaminated than patient areas with the exception of one site where a nurse had an acute exposure during the cleaning-up of an hazardous drug solution spill. In total, 22 urine samples collected from pharmacists and 78 urine samples from nurses had no detectable concentrations of any antineoplastic drugs. Despite the adherence to the recommended safety practices residue contamination on surfaces and floors has continued to be assessed in all the investigated sites.