Синтез и антиинфекционное протективное действие β-циклогексилметил- и β-2-циклогексилэтилгликозидов мурамоилдипептида

Осуществлен синтез β-циклогексилметил- и β-2-циклогексилэтилгликозидов мурамоилдипептида. Исходные перацетилированные β-циклогексилалкилглюкозаминиды были получены оксазолиновым методом. Установлено, что β-циклогексилметил- и β-(2-циклогексилэтил)-МДП обладают высоким антиинфекционным протективным эффектом при поражении мышей летальной дозой Staphylococcus aureus.Здійснено синтез β-циклогексилметил- і β-2-циклогексилетил глікозиді в мурамоїлдипептиду. Вихідні перацетильовані (β-циклогексилалкілглюкозамініди були отримані за оксазоліновим методом. Встановлено, що β-циклогексилметил- і β-(2-циклогексилетил)-МДП володіють високим антиінфекційним протективним ефектом при поразці мишей летальною дозою Staphylococcus aureus.The synthesis of β-cyclohexylmethyl- and β-2-cyclohexylethylglycosides of muramyldipeptide has been carried out. The starting peracetates of β-cyclohexylalkylglucosaminides have been obtained by the oxazoline method. It been found that β-cyclohexylmethyl- and β-(2-cyclohexylethyl)-MDP have a high anti-infection protective effect against the lethal dose of Staphylococcus aureus in mice

Systematic Analysis and Biomarker Study for Alzheimer's Disease.

Revealing the relationship between dysfunctional genes in blood and brain tissues from patients with Alzheimer's Disease (AD) will help us to understand the pathology of this disease. In this study, we conducted the first such large systematic analysis to identify differentially expressed genes (DEGs) in blood samples from 245 AD cases, 143 mild cognitive impairment (MCI) cases, and 182 healthy control subjects, and then compare these with DEGs in brain samples. We evaluated our findings using two independent AD blood datasets and performed a gene-based genome-wide association study to identify potential novel risk genes. We identified 789 and 998 DEGs common to both blood and brain of AD and MCI subjects respectively, over 77% of which had the same regulation directions across tissues and disease status, including the known ABCA7, and the novel TYK2 and TCIRG1. A machine learning classification model containing NDUFA1, MRPL51, and RPL36AL, implicating mitochondrial and ribosomal function, was discovered which discriminated between AD patients and controls with 85.9% of area under the curve and 78.1% accuracy (sensitivity = 77.6%, specificity = 78.9%). Moreover, our findings strongly suggest that mitochondrial dysfunction, NF-κB signalling and iNOS signalling are important dysregulated pathways in AD pathogenesis

Bridging the Mid-Infrared-to-Telecom Gap with Silicon Nanophotonic Spectral Translation

Expanding far beyond traditional applications in optical interconnects at telecommunications wavelengths, the silicon nanophotonic integrated circuit platform has recently proven its merits for working with mid-infrared (mid-IR) optical signals in the 2-8 {\mu}m range. Mid-IR integrated optical systems are capable of addressing applications including industrial process and environmental monitoring, threat detection, medical diagnostics, and free-space communication. Rapid progress has led to the demonstration of various silicon components designed for the on-chip processing of mid-IR signals, including waveguides, vertical grating couplers, microcavities, and electrooptic modulators. Even so, a notable obstacle to the continued advancement of chip-scale systems is imposed by the narrow-bandgap semiconductors, such as InSb and HgCdTe, traditionally used to convert mid-IR photons to electrical currents. The cryogenic or multi-stage thermo-electric cooling required to suppress dark current noise, exponentially dependent upon the ratio Eg/kT, can limit the development of small, low-power, and low-cost integrated optical systems for the mid-IR. However, if the mid-IR optical signal could be spectrally translated to shorter wavelengths, for example within the near-infrared telecom band, photodetectors using wider bandgap semiconductors such as InGaAs or Ge could be used to eliminate prohibitive cooling requirements. Moreover, telecom band detectors typically perform with higher detectivity and faster response times when compared with their mid-IR counterparts. Here we address these challenges with a silicon-integrated approach to spectral translation, by employing efficient four-wave mixing (FWM) and large optical parametric gain in silicon nanophotonic wires

Evaluation of changes in postnatal care using the "Parents' Postnatal Sense of Security" instrument and an assessment of the instrument's reliability and validity

<p>Abstract</p> <p>Background</p> <p>A sense of security is important for experiences of parenthood in the early postpartum period. The objectives of this study were to evaluate two models of postnatal care using a questionnaire incorporating the Parents' Postpartum Sense of Security (<it>PPSS</it>) instrument and to test the validity of the <it>PPSS </it>instrument.</p> <p>Methods</p> <p>Postal surveys were sent to 234 mothers who had experienced two different forms of postnatal care (study group and control group) and returned by 86.8%. These two groups of mothers were compared for total scores on the <it>PPSS </it>instrument. Demographic variables and mothers' opinions about care interventions were also compared and these variables were tested for correlations with the total <it>PPSS </it>score. A regression analysis was carried out to assess areas of midwifery care which might affect a sense of security. The internal consistency and concurrent validity of the instrument were tested for the total population.</p> <p>Results</p> <p>there were no significant differences between the groups for scores on the <it>PPSS </it>instrument. A total of three variables predicted 26% of the variability on the <it>PPSS </it>scores for the study group and five variables predicted 37% of the variability in the control group. One variable was common to both: "<it>The midwives on the postnatal ward paid attention to the mother as an individual"</it>. There were significant correlations between the total <it>PPSS </it>scores and scores for postpartum talks and visits to the breastfeeding clinic. There was also a significant correlation between the single question: "<it>I felt secure during the first postpartum week</it>" and the total <it>PPSS </it>score. Tests for internal consistency and concurrent validity were satisfactory.</p> <p>Conclusion</p> <p>The proposed new model of care neither improved nor impaired mothers' feelings of security the week following birth. Being seen as an individual by the midwife who provides postnatal care may be an important variable for mothers' sense of postnatal security. It is possible that postpartum talks may encourage the processing of childbirth experiences in a positive direction. Availability of breastfeeding support may also add to a sense of security postpartum. The <it>PPSS </it>instrument has shown acceptable reliability and validity.</p

Активизация борьбы с религиозным подпольем накануне Олимпийских игр 1980 года (на материалах Крыма)

In order to make European regions more resilient to flood risks a broadening of Flood Risk Management strategies (FRMSs) might be necessary. The development and implementation of FRMSs like risk prevention, flood defence, mitigation, preparation and recovery is a matter of governance, a process of more or less institutionalized interaction between public and/or private entities ultimately aiming at the realization of collective goals. Such processes are institutionally embedded in Flood Risk Governance Arrangements (FRGAs), which can be defined as “the constellation resulting from a dynamic interplay between actors and actor coalitions involved in all policy domains relevant for Flood Risk Management – including water management, spatial planning and disaster management; their dominant discourses; formal and informal rules of the game; and the power and resource base of the actors involved”. This definition stresses that FRGAs have an actor dimension, a rule dimension, a power and resource dimension and a discursive dimension. By focussing on FRGAs we hope to get a better insight into the societal aspects of FRMSs and the way they are institutionally embedded in a broad sense. The concept allows us to combine insights from policy scientists as well as legal scholars and urges researchers to focus on FRMSs using combined perspectives. The aim of this report is twofold. First we want to explore the governance challenges a shift in FRMSs may pose to society and second we will identify questions for further research. The report is based on a first exploration of relevant scientific articles and reports. Governance challenges are found within each of the four dimensions of the FRGAs. We therefore discuss these dimensions in separate chapters. Major challenges in the actor dimension are the necessity to organise joint working between relevant actors in an effective way, to adequately involve stakeholders and to optimise the science-policy interface. In the rule dimension we have found that the major challenge concerns the translation of general Flood Risk Management principles into a set of more specific organisational, substantive and procedural provisions. Efficient and joint use of resources is the major challenge addressed under the power and resources dimension. The overarching discourse-related governance challenge is the realisation of a discursive shift. Overall, our exploration indicates that FRGAs tend to be highly fragmented. The overall challenge flood risk governance has to face is the development and implementation of inspiring bridging concepts which change agents may use to create synergies between key actors involved in flood risk governance. Concepts like Integrated Water Resources Management (IWRM) or climate proofing are examples of this. Empirical research is needed to further elaborate on this

Factor structure and validity of the shoulder pain and disability index in a population-based study of people with shoulder symptoms

Background: The Shoulder Pain and Disability Index (SPADI) is a self-administered questionnaire that aims to measure pain and disability associated with shoulder disease. The aim of the present study was to investigate the construct validity and factor structure of the SPADI in a population-based study of patients with self-reported chronic shoulder symptoms. Methods: The North West Adelaide Health Study is a representative longitudinal cohort study of people aged 18 years and over. The original sample was randomly selected and recruited by telephone interview. Overall, 3 206 participants returned to the clinic during the second stage (2004-2006) and were asked to report whether they had pain, aching or stiffness on most days in either of their shoulders. Data was also collected on body mass index and shoulder range of motion (ROM) and demographic factors. The SPADI (numeric rating scale) was administered to participants with shoulder symptoms. Principal components factor analysis, with varimax rotation of factor loadings, was used to assess subscale structure of SPADI. Correlations between the SPADI, shoulder ROM and SF-36 were performed. Results: Overall, 22.3% of participants indicated that they had pain, aching or stiffness in either of their shoulders. SPADI results were available for 588 of participants with current shoulder symptoms. The internal consistency of the SPADI subscales were high (Cronbach's alpha > 0.92). Two factors, explaining 61.4% of the total variance were extracted by factor analysis. These were interpreted as disability and pain respectively. There was a strong negative correlation between SPADI disability subscale scores and shoulder range of motion. SPADI disability, but not pain, subscale scores were correlated with age. Conclusions: The SPADI is a valid measure to assess pain and disability in people with shoulder pain in a population-based study. In this setting, the SPADI had a bidimensional structure with both pain and disability subscales.Catherine L Hill, Susan Lester, Anne W Taylor, Michael E Shanahan, Tiffany K Gil

The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia

Molecular genetic analysis offers opportunities to advance our understanding of the nosological relationship between psychiatric diagnostic categories in general, and the mood and psychotic disorders in particular. Strong evidence (P=7.0 × 10−7) of association at the polymorphism rs1006737 (within CACNA1C, the gene encoding the α-1C subunit of the L-type voltage-gated calcium channel) with the risk of bipolar disorder (BD) has recently been reported in a meta-analysis of three genome-wide association studies of BD, including our BD sample (N=1868) studied within the Wellcome Trust Case Control Consortium. Here, we have used our UK case samples of recurrent major depression (N=1196) and schizophrenia (N=479) and UK non-psychiatric comparison groups (N=15316) to examine the spectrum of phenotypic effect of the bipolar risk allele at rs1006737. We found that the risk allele conferred increased risk for schizophrenia (P=0.034) and recurrent major depression (P=0.013) with similar effect sizes to those previously observed in BD (allelic odds ratio ∼1.15). Our findings are evidence of some degree of overlap in the biological underpinnings of susceptibility to mental illness across the clinical spectrum of mood and psychotic disorders, and show that at least some loci can have a relatively general effect on susceptibility to diagnostic categories, as currently defined. Our findings will contribute to a better understanding of the pathogenesis of major psychiatric illness, and such knowledge should be useful in providing an etiological rationale for shaping psychiatric nosology, which is currently reliant entirely on descriptive clinical data

The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients – a multicenter randomized study

Background: Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. Methods: Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. Results: A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 [plus or minus] 45 IU/L and 55 [plus or minus] 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. Conclusion: Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.Funding for this study was provided by McNeil Consumer Healthcare to the Denver Health Authority, Denver, Colorado

EEG Correlates of Attentional Load during Multiple Object Tracking

While human subjects tracked a subset of ten identical, randomly-moving objects, event-related potentials (ERPs) were evoked at parieto-occipital sites by task-irrelevant flashes that were superimposed on either tracked (Target) or non-tracked (Distractor) objects. With ERPs as markers of attention, we investigated how allocation of attention varied with tracking load, that is, with the number of objects that were tracked. Flashes on Target discs elicited stronger ERPs than did flashes on Distractor discs; ERP amplitude (0–250 ms) decreased monotonically as load increased from two to three to four (of ten) discs. Amplitude decreased more rapidly for Target discs than Distractor discs. As a result, with increasing tracking loads, the difference between ERPs to Targets and Distractors diminished. This change in ERP amplitudes with load accords well with behavioral performance, suggesting that successful tracking depends upon the relationship between the neural signals associated with attended and non-attended objects