The advancement of scientific and medical research over the past years has generated a wealth of experimental data from multiple technologies, including genomics, transcriptomics, proteomics and other forms of -omics data, which are available for a number of diseases. The integration of such multisource data is a key component towards the success of precision medicine. In this work we are investigating a multisource data integration method developed by our group, regarding its ability to drive to clusters of connected pathways under two different approaches: (a) a disease-centric approach, where we want to integrate data around a disease, and (b) a gene-centric approach, where we want to integrate data around a gene. We have used as a paradigm for the first approach Huntington's disease (HD), a disease with a plethora of available data, whereas for the second approach the GBA2, a gene that is related to Spastic Ataxia (SA), a phenotype with sparse availability of data. Our work shows that valuable information at the level of disease-related pathway clusters can be obtained for both HD and SA. New pathways that classical pathway analysis methods were unable to reveal, are emerging as necessary "connectors" to build connected pathway stories formed as pathway clusters.

A restriction endonuclease analysis of the hemolytic plasmid pSU316 has allowed location of the cleavage sites for the endonucleases BamHI, XbaI, KpnI, Bg/II, Sa/GI, EcoRI, and HindIII. Hybridization experiments between pSU316 and pED100 have shown that the tra region of pSU316 lies in a segment comprising part of Sa/GI fragments S-1 and S-3 and the entire fragment S-4. The positions of other plasmids coded functions, namely the replication functions and alpha-hemolysin production, have been determined in the physical map.

This study explored the roles of referent power (i.e., influence based on sense of identification) and expert power (i.e., influence based on knowledge and expertise) in Schizophrenics Anonymous (SA), a mutual-help group for persons experiencing a schizophrenia-related illness. The study describes SA participants' experience of referent and expert power with SA members, SA leaders, and with mental health professionals. It also examines whether or not referent and expert power ascribed to fellow SA participants predicts the perceived helpfulness of the group. One hundred fifty-six SA participants were surveyed. Participants reported experiencing higher levels of referent power with fellow SA members and leaders than with mental health professionals. They reported higher levels of expert power for mental health professionals and SA leaders than for SA members. The respondents' ratings of their SA group's helpfulness was significantly correlated with ratings of referent and expert power. Although expert power was the best independent predictor of helpfulness, a significant interaction between referent and expert power indicated that when members reported high referent power, expert power was not related to helpfulness. These results are interpreted to suggest that there are multiple forms of social influence at work in mutual help.

Comparative analysis of metagenomes can be used to detect sub-metagenomes (species or gene sets) that are associated with specific phenotypes (e.g., host status). The typical workflow is to assemble and annotate metagenomic datasets individually or as a whole, followed by statistical tests to identify differentially abundant species/genes. We previously developed subtractive assembly (SA), a de novo assembly approach for comparative metagenomics that first detects differential reads that distinguish between two groups of metagenomes and then only assembles these reads. Application of SA to type 2 diabetes (T2D) microbiomes revealed new microbial genes associated with T2D. Here we further developed a Concurrent Subtractive Assembly (CoSA) approach, which uses a Wilcoxon rank-sum (WRS) test to detect k-mers that are differentially abundant between two groups of microbiomes (by contrast, SA only checks ratios of k-mer counts in one pooled sample versus the other). It then uses identified differential k-mers to extract reads that are likely sequenced from the sub-metagenome with consistent abundance differences between the groups of microbiomes. Further, CoSA attempts to reduce the redundancy of reads (from abundant common species) by excluding reads containing abundant k-mers. Using simulated microbiome datasets and T2D datasets, we show that CoSA achieves strikingly better performance in detecting consistent changes than SA does, and it enables the detection and assembly of genomes and genes with minor abundance difference. A SVM classifier built upon the microbial genes detected by CoSA from the T2D datasets can accurately discriminates patients from healthy controls, with an AUC of 0.94 (10-fold cross-validation), and therefore these differential genes (207 genes) may serve as potential microbial marker genes for T2D.

Polyelectrolyte microcapsules have great potential for serving as carriers for the delivery of their contents when triggered by an external stimulus. Aptamers are synthetic ssDNA or RNA that can bind to specific targets with high affinity and selectivity. Aptamers may retain these superior molecular recognition properties after encapsulation within polymer microcapsules. In this work, stable polyelectrolyte microcapsules with encapsulated aptamers were obtained by the layer-by-layer (LbL) method. Polyelectrolyte films were deposited onto a CaCO3 template that had been predoped with polystyrene sulfonate (PSS) and aptamer sequences (SA) that have an affinity for the dye sulforhodamine B (SRB). The PSS and aptamers are thought to serve as an internal scaffold supporting the microcapsule walls. These microcapsules would present target-molecule-triggered rupture properties. Microcapsule collapse was triggered by the binding of SRB to the encapsulated aptamer. The specificity of microcapsule collapse was investigated using a similar dye, tetramethylrosamine (TMR), which does not have affinity for SA. A high concentration of TMR did not lead to the collapse of the microcapsules. The effect of target binding on the microcapsules was confirmed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). These microcapsules may have potential applications in targeted delivery systems for the controlled release of drugs, pesticides, or other payloads.

Cortical microinfarcts (CoMIs) are considered as barely visible lesions in clinical-neuroradiological correlation studies. On postmortem 7.0-tesla MRI, however, CoMIs of different size are easily detected.

The present MRI study investigates 84 postmortem brains with different neurodegenerative diseases and vascular dementia (VaD) for their topographic distribution and the prevalence of CoMIs. The mean numbers of CoMIs were determined on 6 hemispheric coronal sections and in 22 different gyri with a 7.0-tesla MRI Bruker BioSpin SA. A large coronal section at the level of the mammillary body was also used for neuropathological evaluation. CoMIs were predominantly observed in the prefrontal and postcentral sections of VaD brains. The mean number of CoMIs was significantly increased in the inferior frontal and in the cingulate gyri of VaD brains compared to the controls. No topographic differences were observed in the neurodegenerative diseases.

As the inferior frontal and the cingulated gyri are areas frequently involved in VaD, CoMIs in those strategic locations must have an impact on the evolution of the vascular cognitive decline in those patients.

OBJECTIVE

Condition-specific sexual questionnaires are essential for clinical trials and important patient-reported outcome measures. The aim of the study was to translate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association Revised (PISQ-IR) into German and to clinically validate it in a German-speaking population.

METHODS

The translated PISQ-IR was linguistically validated in two rounds of cognitive interviews. The final instrument was psychometrically validated in women presenting to urogynecological clinics with pelvic floor dysfunction. For analysis of criterion validity, three related self-reported measures were administered: the Female Sexual Function Index (FSFI), the Kings Health Questionnaire (KHQ), and the 36-Item Short Form Health Survey (SF-36). For external validity, PISQ-IR subscales were compared to the clinical-measures Pelvic Organ Prolapse Quantification system (POP-Q) stage, pelvic floor muscle tone, and Oxford Grading Scale. Descriptive statistics, floor and ceiling effects, internal consistency using Cronbach's alpha coefficient, and Pearson correlations were calculated for all PISQ-IR subscales.

RESULTS

The PISQ-IR was completed by 197 women, out of whom 66 (33.5 %) considered themselves not sexually active (NSA) and 131 (66.5 %) as sexually active (SA). Participants' mean age was 57 ± 12 years; 50 % were diagnosed with symptomatic POP, 74 % with urinary incontinence (UI) and 4 % with anal incontinence (AI). The PISQ-IR subscales were analyzed separately for SA and NSA women with Cronbach's alpha coefficients ranging from 0.64 to 0.94. Moderate to high correlations were observed between PISQ-IR subscales and related quality of life (QoL) scales and corresponding FSFI scales.

CONCLUSIONS

Initial testing of the German PISQ-IR suggests it is an internally consistent and valid tool for use in clinical practice and research.

Serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) were measured in serum samples of 1,964 pregnant Japanese women whose gestational age and singleton pregnancy were confirmed by ultrasound examination during the first trimester of pregnancy. Statistical analysis of log-linear regression to calculate multiples of the median (MoM) was accomplished by the SAS statistical method. The levels of the two analytes noticeably decreased as maternal body weight increased. However, maternal age did not have a significant effect on either of them. The MoM formulae were as follows: MSAFPMoM = AFP/exp(0.861 + 0.0685 x gestational age(weeks) - 0.00572 x body weight(kg)). MShCGMoM = hCG/exp(6.12 - 0.787 x gestational age(weeks) - 0.00613 x body weight(kg)). Gestational age and maternal body weight should be considered as regression functions for the adjustment of serum levels in risk estimation of fetal anomalies and fetal demise in Japan.

OBJECTIVE

Main aim: to determine the frequency of violence in primary care. Secondary aims: to analyse its causes, consequences and connection with professional burnout and reduced motivation.

METHODS

Transversal, descriptive study.

METHODS

Primary care.

METHODS

68 primary care doctors from 4 districts in the province of Jaén (350, 19%).

METHODS

Self-administered questionnaire with an ad hoc design, sent out by mail and including personal and job details and doctors' views on the causes and consequences of burnout and violence, and the attitudes of the Andalusian Health Service (SAS) and professional bodies (overall reliability, Cronbach's alpha =.7898).

RESULTS

58% had suffered aggression (85% verbal abuse, 67.5% threats, 12.5% physical aggression). Being attacked was linked with attributing the responsibility to the patients (odds ratio [OR]=7.6, 95% confidence interval [CI], 2.5-23), with doing extra shifts (OR=6.3; 95% CI, 1.2-33), rigidity (OR=3.5; 95% CI, 1.2-10.7), inadequate handling of emotive situations (OR=3.2; 95% CI, 1.1-9.2,) and incompetence (OR=5.2; 95% CI, 1.6-17). Violence scored the lowest as cause of burnout and was linked to the job being less rewarding (OR=2.9; 95% CI, 1.0-7.8). It was linked to irritation with the SAS (OR=2.8; 95% CI, 1.0-7.5) and fear of reduced motivation (OR=2.8; 95% CI, 1.0-7.5), with this latter being linked to loss of social prestige (P<.01), feeling low self-esteem (P<.01), and depression (P<.01).

CONCLUSIONS

Violence is more common than in the figures given by the International Labour Organisation. It is associated with distrust, lack of communication in health care delivery and incompetence. It is the cause of burnout that is least appreciated and it is linked to the job being less rewarding and to greater fear of reduced motivation.

The mechanism behind stretch activation (SA), a mechanical property that increases muscle force and oscillatory power generation, is not known. We used Drosophila transgenic techniques and our new muscle preparation, the jump muscle, to determine if myosin heavy chain isoforms influence the magnitude and rate of SA force generation. We found that Drosophila jump muscles show very low SA force and cannot produce positive power under oscillatory conditions at pCa 5.0. However, we transformed the jump muscle to be moderately stretch-activatable by replacing its myosin isoform with an embryonic isoform (EMB). Expressing EMB, jump muscle SA force increased by 163% and it generated net positive power. The rate of SA force development decreased by 58% with EMB expression. Power generation is Pi dependent as >4 mM Pi was required for positive power from EMB. Pi increased EMB SA force, but not wild-type SA force. Our data suggest that when muscle expressing EMB is stretched, EMB is more easily driven backward to a weakly bound state than wild-type jump muscle. This increases the number of myosin heads available to rapidly bind to actin and contribute to SA force generation. We conclude that myosin heavy chain isoforms influence both SA kinetics and SA force, which can determine if a muscle is capable of generating oscillatory power at a fixed calcium concentration.

We studied by autoradiography the distribution of 45Ca in the enamel organ of frozen rats 4.3, 6.1, 7.8, 10.6 and 13.7 sec after an i.v. injection. The intercellular junctions of the proximal side of the smooth-ended ameloblast (SA) and the distal side of the ruffle-ended ameloblast (RA) were closed to calcium. The junctions of the distal side of SA, the proximal side of RA, and both sides of the secretory stage ameloblasts were not. The time required for calcium to pass through the ameloblast layer was less than 1.8 sec in the secretory stage and SA region. The time in the RA region was 3.5-6.3 sec. In the transitional region from RA to SA, a band of strong radioactivity appeared from the papillary layer of RA region towards the enamel of the SA region. The radioactivity in the secretory stage enamel increased almost linearly with time. The diffusion speed of calcium in the enamel was more than 50 microns for 1.8 sec in the maturation stage and less than 15 microns for 9.4 sec in the secretory stage. These results indicate that in the secretory and SA regions calcium moves to the enamel surface through the intercellular spaces of ameloblasts and in the RA region via RA cells.

BACKGROUND

Bleeding from the popular clean-shave 'chiskop' haircut was recently reported as prevalent in South Africa (SA), a country with 6.9 million HIV-infected people.

OBJECTIVE

To investigate the prevalence of barber hair clipper contamination with blood and HIV and hepatitis B viruses.

METHODS

Fifty barbers from three townships in Cape Town, SA, were invited to participate. One clipper from each barber was collected immediately after it had been used for a clean-shave haircut. Each clipper was rinsed with phosphate-buffered saline and then submerged in viral medium. The polymerase chain reaction (PCR) was used to identify the blood-specific RNA marker haemoglobin beta (HBB), hepatitis B virus (HBV) and HIV.

RESULTS

The clean-shave haircut was the most common haircut requested by clients (78%). Of the clippers collected, 42% were positive for HBB, confirming detection of blood, none were positive for HIV, and 4 (8%) were positive for HBV. Two clippers (clippers 16 and 20) were positive on qualitative HBV PCR. HBV DNA from clipper 16 clustered with genotype A sequences from SA, India, Brazil and Martinique, while clipper 20 clustered with SA genotype D sequences. The clipper 20 sequence was identical to a subtype D sequence (GenBank accession AY233291) from Gauteng, SA.

CONCLUSIONS

This study confirms that there is significant contamination of barber hair clippers with blood and blood-borne viruses. Hepatitis B was detected with enough DNA copies to pose a risk of transmitting infection. Although HIV was not detected in this small study, the risk of transmission should be quantified. Further studies to investigate barber clipper sterilisation practices and whether the clean-shave hairstyle is an independent risk factor for HIV, HBV and hepatitis C virus infections are warranted. Public education on individual clipper ownership (as is the case with a toothbrush) should be advocated for clean-shave and blade-fade haircuts.

BACKGROUND

Quantitative and Qualitative studies have been widely used in isolation to estimate several associations in developing countries, but little is known about combining both methods in a given study and ascertains validity.

OBJECTIVE

The objective of the following study was to accurately measure the constructs and to check for the internal consistency whereas measuring occupational stress among software professionals. We compared contextual stressors developed from the qualitative study with occupational stress index (OSI) among Information Technology/Information Technology Enabled Service (IT/ITES) professionals in India.

METHODS

We employed mixed methods sampling strategy for selecting the IT/ITES professionals for the study. The first stage involved a qualitative study followed by a cross-sectional study among 1071 workers in the IT and ITES sector in Bengaluru.

METHODS

There were two types of stress domains used in the questionnaire. First, contextual stress domains, which were constructed based on the results of the qualitative study. Second, we used OSI for computer workers.

METHODS

Data from the cross sectional survey was analyzed using SAS 9.1.(SAS Institute Inc., Cary, NC, USA). We used Cronbach's coefficient alpha for analyzing latent constructs of OSI and contextual stress domains.

RESULTS

The results indicate that OSI doesn't correlate well with contextual stressors.

CONCLUSIONS

OSI is a generic questionnaire designed for a computer worker and using the contextual stressors based on the results from the qualitative study might capture the occupational stressors more reliably.

We characterized protective immune response in mice infected with the attenuated Japanese encephalitis virus (JEV) strain SA(A) derived from the live JE vaccine strain SASA(A), antibodies to JEV envelope (E) and non-structural NS1 proteins were detected by Western blot analysis and neutralization, haemagglutination-inhibition (HAI), and complement fixation (CF) antibodies were detected by serological tests. Production of antibody to NS1 protein strongly indicated peripheral growth of SA(A) in mice and its growth induced the immune response. A single immunization with SA(A) significantly protected mice against lethal intracerebral (ic) challenge with the virulent SA(V) strain.

A growing body of evidence indicates that excessive sugar consumption is driving epidemics of obesity and related non-communicable diseases (NCDs) around the world. South Africa (SA), a major consumer of sugar, is also the third most obese country in Africa, and 40% of all deaths in the country result from NCDs. A number of fiscal, regulatory, and legislative levers could reduce sugar consumption in SA. This paper focuses on a sugar-sweetened beverage (SSB) tax. The purpose of the paper is to highlight the challenges that government might anticipate. Policies cannot be enacted in a vacuum and discussion is focused on the industrial, economic, and societal context. The affected industry actors have been part of the SA economy for over a century and remain influential. To deflect attention, the sugar industry can be expected either to advocate for self-regulation or to promote public-private partnerships. This paper cautions against both approaches as evidence suggests that they will be ineffective in curbing the negative health impacts caused by excessive sugar consumption. In summary, policy needs to be introduced with a political strategy sensitive to the various interests at stake. In particular, the sugar industry can be expected to be resistant to the introduction of any type of tax on SSBs.

OBJECTIVE

To determine the sensitivity and specificity of clinical and laboratory signs for the diagnosis of septic arthritis (SA). Patients and methods This prospective study included all adult patients with suspected SA seen in the emergency department or rheumatology department at the University Hospital, Clermont-Ferrand, France, over a period of 18 months.

RESULTS

In total, 105 patients with suspected SA were included, 38 (36%) presenting with SA (29 [28%] with bacteriologically documented SA). In the univariate analysis, chills (p=0.015), gradual onset (p=0.04), local redness (p=0.01), as well as an entry site for infection (p=0.01) were most often identified in SA. A history of crystal-induced arthritis (p=0.004) was more frequent in non-SA cases. An erythrocyte sedimentation rate (ESR)>50 mm (p=0.005), a C-reactive protein (CRP) level >100 mg/L (p=0.019), and radiological signs suggestive of SA (p=0.001) were more frequent in the SA cases. Synovial fluid appearance: purulent (p50,000/μL (p < 0.001), differentiated between SA and non-SA. In multivariate analysis, only chills (odds ration [OR]=4.7, 95% confidence interval [CI] 1.3-17.1), a history of crystal-induced arthritis (OR=0.09, 95% CI 0.01-0.9), purulent appearance of the joint fluid (OR=8.4, 95% CI 2.4-28.5), synovial WBC count >50,000/mm3 (OR=6.8, 95% CI 1.3-36), and radiological findings (OR=7.1, 95% CI 13-37.9) remained significant.

CONCLUSIONS

No clinical sign or laboratory test (excluding bacteriological test), taken alone, is conclusive for the differentiation between SA and non-SA, but the association of several signs, notably chills, history of crystal-induced arthritis, radiological findings, and the appearance and cellularity of joint fluid may be suggestive.

Systemic administration of salicylate (SA) to rats (100 mg kg-1 i.p. ) was used as an in vivo trap of hydroxyl radicals (.OH). In the brain SA reacts with hydroxyl radicals to form the stable adducts 2, 3- and 2,5 dihydroxybenzoic acid (DHBAs) which can thus be taken as an index of .OH formation. The DHBAs were recovered by intracerebral microdialysis in hippocampus or striatum and quantified by high pressure liquid chromatography (HPLC) with electrochemical detection. There were no peaks corresponding to 2,5-DHBA or 2,3-DHBA in the chromatograms from rats not receiving SA. A basal level of 2,5-DHBA was seen in the dialysates from all animals given SA whereas 2, 3-DHBA was not detected. In one group of rats generation of free oxygen radicals was induced in the striatum by adding Fe2+ and ascorbate to the perfusion fluid to test the sensitivity of the system. Addition of Fe2+ ascorbate to the perfusion fluid induced a significant 7-fold increase in 2,5-DHBA that gradually returned to baseline after removal of Fe2+/ascorbate. In two other groups the microdialysis probes were implanted in either the striatum or the hippocampus and the animals were subjected to 20 min of four-vessel occlusion + hypotension (4-VOH). Significant reductions in 2,5-DHBA were detected during ischaemia followed by significant increases of 5-fold and 3-fold in the striatum and hippocampus, respectively, beginning immediately upon reperfusion and lasting for the remainder of the observation period (160 min).

Arsenic is an environmental pollutant, and its liver toxicity has long been recognized. The effect of arsenic on liver protein expression was analyzed using a proteomic approach in monkeys. Monkeys were orally administered sodium arsenite (SA) for 28 days. As shown by 2D-PAGE in combination with MS, the expression levels of 16 proteins were quantitatively changed in SA-treated monkey livers compared to control-treated monkey livers. Specifically, the levels of two proteins, mortalin and tubulin beta chain, were increased, and 14 were decreased, including plastin-3, cystathionine-beta-synthase, selenium-binding protein 1, annexin A6, alpha-enolase, phosphoenolpyruvate carboxykinase-M, erlin-2, and arginase-1. In view of their functional roles, differential expression of these proteins may contribute to arsenic-induced liver toxicity, including cell death and carcinogenesis. Among the 16 identified proteins, four were selected for validation by Western blot and immunohistochemistry. Additional Western blot analyses indicated arsenic-induced dysregulation of oxidative stress related, genotoxicity-related, and glucose metabolism related proteins in livers from SA-treated animals. Many changes in the abundance of toxicity-related proteins were also demonstrated in SA-treated human hepatoma cells. These data on the arsenic-induced regulation of proteins with critical roles may help elucidate the specific mechanisms underlying arsenic-induced liver toxicity.

Inorganic arsenic (i-As) is a naturally occurring toxic metalloid affecting millions of people worldwide. It is known to be carcinogen, liver being a potential target, and related to the prevalence of diabetes in arseniasis-endemic areas. Hepatocyte nuclear factor 1 and 4 alpha (HNF1α and HNF4α) are key members of a transcriptional network essential for normal liver architecture. Changes in HNF1α and HNF4α expression are clearly associated with the development of liver malignancies and diabetes in humans. In this work, hepatic HepG2 cells and golden Syrian hamsters were exposed to sub-toxic, environmentally relevant doses of sodium arsenite (SA; up to 10 μM in vitro, 15 mg/L in vivo) in order to evaluate whether arsenic is able to compromise the expression of hepatocyte nuclear factors. Also, liver histopathological examination was carried out, and several markers of hepatocyte differentiation and glucose metabolism status were determined as a measure of i-As-induced effects. Results show a consistent down-regulation of HNF1α and HNF4α under a scenario of exposure where HepG2 cells (1) gained resistance to arsenic-induced toxicity/apoptosis, (2) attained loss of tissue-specific features (as shown by the observed down-regulation of ALDOB, PEPCK and CYP1A2, triggering of the epithelial-to-mesenchymal transition program and the hypersecretion of matrix metalloproteinase-2 and 9), (3) failed to maintain balanced expression of the "stemness" genes C-MYC, OCT3/4, LIN28 and NOTCH2 and (4) showed glucose metabolism impairment. We conclude that the i-As-induced down-regulation of HNF1α and HNF4α under chronic settings may play a central role in the features of disease and cancer observed both in vivo and in vitro.

OBJECTIVE

Fatal familial insomnia (FFI) is linked to a mutation at codon 178 (C178) of the prion protein gene (PRNP). FFI is pathologically characterized by selective atrophy of the anteroventral and mediodorsal thalamic nuclei and clinically by loss of sleep, dysautonomia and motor signs. A key early polysomnographic sign of the disease onset is the loss of sleep spindling (sigma activity, SA). In FFI the loss of SA leads to the spectral representation of a sudden slow wave activity (SWA) increase from an awake state, the reaching of a stable plateau without oscillations, followed by abrupt fall down to REM sleep. We evaluated the presence of differences in the spectral sleep EEG pattern in FFI relatives carriers (C178(pos)) or non-carriers (C178(neg)) of the C178 mutation.

METHODS

Seventeen healthy relatives of FFI patients, 8 carriers of the C178 FFI mutation in a preclinical condition and 9 non carriers, underwent two-night polysomnography. The absolute and relative EEG power of the 4 main bands (delta: SWA, 0.5-4.0 Hz; theta: TB, 4.5-8 Hz; alpha: AB, 8.5-12 Hz; sigma: SA, 12.5-16 Hz) has been studied for the total sleep time, the period of delta increase after sleep onset, and the period of delta plateau. Multiple regression has been applied to investigate relations between the power of the bands studied and 3 parameters: age, the gender of the subjects and the C178 genotype.

RESULTS

Our study could not show evidence of differences in the sleep EEG composition between carriers and non-carriers of the C178 FFI mutation.

CONCLUSIONS

The spectral analysis techniques we used were not able to disclose sleep EEG markers linked to the FFI C178(pos) in the preclinical condition. Key sleep EEG alteration become evident only at the clinical onset of the disease.

We use the H-Pex (Thomas et al., this issue) to analyze the main chain interactions in 131 proteins. In antiparallel beta-sheets, the geometry of the N...O bond is: median N...O distances, 2.9 SA, C==O...N angles at 154 degrees and the C alpha--C==O...H angles are dispersed around 3 degrees. In some instances, the other side of the C==O axis is occupied by a HC alpha. As recently supported by Vargas et al. (J Am Chem Soc 2000;122:4750-4755) C alpha H...O and NH...O could cooperate to sheet stability. In alpha-helices, the main chain C==O interact with the NH of their n + 4 neighbor on one side, and with a C beta H or C gamma H on the other side. The median O...N distance (3.0 A) and C==N angle (147 degrees) suggest a canonical H-bond, but the C alpha--C==O...H dihedral angle invalidates this option, since the hydrogen attacks the oxygen at 122 degrees, i.e., between the sp(2) and pi orbitals. This supports that the H-bond is noncanonical. In many instances, the C gamma H or the C beta H of the n + 4 residue stands opposite to the NH with respect to the oxygen. Therefore, we propose that, in alpha-helices, the C gamma H or C beta H and the NH of the n + 4 residue hold the oxygen like an electrostatic pincher. Proteins 2001;43:37-44.

We investigated the effect of SAS on the long term memory in PD patients and compared them with patients with brain infarction or cataract (control group), respectively. PD patients develop SAS and cognitive impairments more often then healthy people. Since SAS leads to a fragmentation of the sleep structure it interferes with memory. Therefore SAS may be a pathogenic factor of cognitive impairment in PD. We studied 14 patients (7 with and 7 without SAS) with PD, brain infarction or cataract using the LGT-3, which measures the verbal, numeric and figural long term memory. All patients answered subtest 7 of the Wechsler-Memory-Scale at night and in the morning. The saving between the evening and morning measure was calculated. An analysis of variance was performed using the SAS-condition and the different groups as independent variable. A significant difference (p < or = 0.005) of all memory measurements between patients with and without SAS but not between the different groups has been proved with a superiority of the patients without SAS. A significant difference of the influence of the SAS for verbal memory score on patients with PD (pp < or = 0.05) and brain infarction (pp < or = 0.005) respectively and the control group could be demonstrated. Therefore we found a quantitative difference of memory consolidation in PD patients with SAS. The influence of SAS on memory in patients with neurological disease is more pronounced compared to the control group.

BACKGROUND

Neuroimaging studies suggest that social distress and suicidal vulnerability share common cerebral bases. Moreover, increased peripheral inflammatory activity is involved in both social distress and suicidal behavior.

OBJECTIVE

To evaluate, in suicidal and non-suicidal individuals, the association between the activation of specific cerebral regions (anterior cingulate, insula and orbitofrontal cortex) during experimental social exclusion and the baseline blood levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) and of the anti-inflammatory cytokine interleukin-2 (IL-2).

METHODS

In total, 101 euthymic women were recruited: 42 suicide attempters (SA), 40 affective controls (AC), and 19 healthy controls (HC). During functional MRI (fMRI), they performed the Cyberball game, a validated social exclusion task. Blood levels of IL-1β, IL-6, TNF-α and IL-2 were measured prior to fMRI. The activation of insula, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) during the explicit social exclusion (ESE) vs social inclusion (INC) conditions of the Cyberball game was analyzed in function of the baseline cytokine levels.

RESULTS

IL-1β was negatively associated with right OFC activation (p = 0.01) in ESE vs. INC, whereas IL-2 was positively associated with activation of the right ACC (p = 0.02), insula (p = 0.002) and OFC (p = 0.004) in ESE vs. INC. These associations remained significant after controlling for group, indicating that they were independent of the suicidal status.

CONCLUSIONS

Baseline IL-1β and IL-2 blood levels are differentially associated with cerebral activation involved in the perception of social exclusion, independently of suicidal behavior. Our results may help to better understand the role of basal inflammation in social distress and its link with mood disorder pathophysiology.

This study was aimed to determine the efficacy of multispecies probiotics in reducing the severity of post-weaning diarrhea caused by enterotoxigenic Escherichia coli (ETEC) F18⁺ on newly weaned pigs. Thirty-two pigs (16 barrows and 16 gilts, BW = 6.99 ± 0.33 kg) at 21 d of age were individually allotted in a randomized complete block design with 2 × 2 factorial arrangement of treatments. Pigs were selected from sows not infected previously and not vaccinated against ETEC. Pigs were fed experimental diets for 25 d based on 10 d phase 1 and 15 d phase 2. The factors were ETEC challenge (oral inoculation of saline solution or E. coli F18⁺ at 2 × 10⁹ CFU) and probiotics (none or multispecies probiotics 0.15% and 0.10% for phase 1 and 2, respectively). Body weight and feed intake were measured on d 5, 9, 13, 19, and 25. Fecal scores were measured daily. Blood samples were taken on d 19 and 24. On d 25, all pigs were euthanized to obtain samples of digesta, intestinal tissues, and spleen. The tumor necrosis factor alpha (TNFα), malondialdehyde (MDA), peptide YY (PYY), and neuropeptide Y (NPY) were measured in serum and intestinal tissue. Data were analyzed using the MIXED procedure of SAS. The fecal score of pigs was increased (P < 0.05) by ETEC challenge at the post-challenge period. The ETEC challenge decreased (P < 0.05) jejunal villus height and crypt depth, tended to increase (P = 0.056) jejunal TNFα, increased (P < 0.05) ileal crypt depth, and decreased (P < 0.05) serum NPY. The probiotics decreased (P < 0.05) serum TNFα, tended to reduce (P = 0.064) jejunal MDA, tended to increase (P = 0.092) serum PYY, and increased (P < 0.05) jejunal villus height, and especially villus height-to-crypt depth ratio in challenged pigs. Growth performance of pigs were not affected by ETEC challenge, whereas the probiotics increased (P < 0.05) ADG and ADFI and tended to increase (P = 0.069) G:F ratio. In conclusion, ETEC F18⁺ challenge caused diarrhea, intestinal inflammation and morphological damages without affecting the growth performance. The multispecies probiotics enhanced growth performance by reducing intestinal inflammation, oxidative stress, morphological damages.

Keywords: Escherichia coli; Growth performance; Gut health; Nursery pig; Post-weaning diarrhea; Probiotic.