Acquisition of MDR-GNB in hospital settings: a systematic review and meta-analysis focusing on ESBL-E.

INTRODUCTION: Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and other multi-drug-resistant Gram-negative bacteria (MDR-GNB) have disseminated globally since their discovery in the late 20th century. Various infection prevention and control measures are in place to prevent nosocomial transmission of these organisms, but their efficacy remains disputed. New literature has emerged in recent years providing further evidence which can be used to formulate effective strategies to tackle this issue in the future. METHODS: A systematic review was performed to characterize the prevalence of colonization of multi-drug-resistant organisms and subsequent acquisition of these organisms within hospital settings. A meta-analysis was performed to characterize the prevalence and acquisition of ESBL-E in Europe and North America. RESULTS: Twenty-eight studies fulfilled the inclusion criteria. Escherichia coli formed the main burden of MDR-GNB colonization worldwide. Patient-to-patient transmission of ESBL-E was found to be rare, but increased transmissibility of Klebsiella pneumoniae was described over E. coli. Within European and North American healthcare settings, a meta-analysis of eight studies identified a pooled prevalence of ESBL-E on admission to hospital of 7.91% and an acquisition rate of 3.73%. DISCUSSION: Low prevalence at the point of hospital admission and insufficient evidence of patient-to-patient transmission suggests that infection prevention and control measures such as universal surveillance screening and single-room isolation are unlikely to be practical or effective interventions in reducing the overall burden of ESBL-E in hospitals, in line with current European guidelines. Instead, it is argued that efforts should be placed on controlling the spread of these organisms and other MDR-GNB in the community, predominantly long-term care facilities.

The sensitivity of the QuantiFERON®-TB Gold Plus assay in Zambian adults with active tuberculosis.

SETTING AND OBJECTIVE: To investigate the sensitivity of the new interferon-gamma release assay (IGRA), QuantiFERON®-TB Gold Plus (QFT-Plus), for active TB (used as a surrogate for latent tuberculous infection) in a Zambian TB clinic. DESIGN: Consecutive smear or Xpert® MTB/RIF-positive adult (age 18 years) pulmonary TB patients were recruited between June 2015 and March 2016. Venous blood was tested using QFT-Plus. The sensitivity was defined as the number positive divided by the total number tested. Using logistic regression, factors associated with positive QFT-Plus results were explored. RESULTS: Of 108 patients (median age 32 years, interquartile range 27-38; 73% male; 63% human immunodeficiency virus [HIV] positive), 90 were QFT-Plus-positive, 11 were negative and seven had indeterminate results; sensitivity was 83% (95%CI 75-90). There was no difference in sensitivity by HIV status (HIV-positive 85%, 95%CI 75-93; n = 68 vs. HIV-negative 80%, 95%CI 64-91; n = 40; P = 0.59). In models adjusted for age alone, CD4 cell count <100 cells/µl (OR 0.15, 95%CI 0.02-0.96; P = 0.05) and body mass index <18.5 kg/m2 (OR 0.27, 95%CI 0.08-0.91; P = 0.02) were associated with decreased odds of positive QFT-Plus results. CONCLUSION: Overall, the sensitivity of QFT-Plus is similar to that of the tuberculin skin test and other IGRAs. While overall sensitivity is not affected by HIV status, QFT-Plus sensitivity was lower among people living with HIV/acquired immune-deficiency syndrome with severe immunosuppression.

Association between diabetes mellitus and active tuberculosis in Africa and the effect of HIV.

OBJECTIVE: To determine current evidence for the association between diabetes and active tuberculosis in Africa, and how HIV modifies, or not, any association between diabetes and active tuberculosis. METHODS: We conducted a systematic review by searching the EMBASE, Global Health and MEDLINE databases. Studies were eligible for inclusion if they explored the association between diabetes mellitus prevalence and active tuberculosis incidence or prevalence, used a comparison group, were conducted in an African population and adjusted the analysis for at least age. Study characteristics were compared, and risk of bias was assessed. The range of effect estimates was determined for the primary association and for effect modification by HIV. RESULTS: Three eligible studies were identified: two investigated the primary association and two investigated HIV as a potential effect modifier. All studies were case-control studies, including a combined total of 1958 tuberculosis cases and 2111 non-tuberculosis controls. Diabetes diagnostic methods and analysis strategies varied between studies. Individual study adjusted odds ratios of active tuberculosis for the effect of diabetes mellitus (unstratified) ranged from 0.88 (95% CI 0.17-4.58) to 10.7 (95% CI 4.5-26.0). Individual study P-values for HIV interaction ranged from 0.01 to 0.83. Quantitative synthesis of individual study data was not performed due to heterogeneity between studies. CONCLUSIONS: Few data currently exist on the association between diabetes and active tuberculosis in Africa, and on the effect of HIV on this association. Existing data are disparate. More regional research is needed to guide policy and practice on the care and control of tuberculosis and diabetes in Africa.

Measurement of the parity-violating asymmetry in inclusive electroproduction of π- near the Δ0 resonance.

The parity-violating (PV) asymmetry of inclusive π- production in electron scattering from a liquid deuterium target was measured at backward angles. The measurement was conducted as a part of the G0 experiment, at a beam energy of 360 MeV. The physics process dominating pion production for these kinematics is quasifree photoproduction off the neutron via the Δ0 resonance. In the context of heavy-baryon chiral perturbation theory, this asymmetry is related to a low-energy constant d(Δ)- that characterizes the parity-violating γNΔ coupling. Zhu et al. calculated d(Δ)- in a model benchmarked by the large asymmetries seen in hyperon weak radiative decays, and predicted potentially large asymmetries for this process, ranging from A(γ)-=-5.2 to +5.2 ppm. The measurement performed in this work leads to A(γ)-=-0.36±1.06±0.37±0.03 ppm (where sources of statistical, systematic and theoretical uncertainties are included), which would disfavor enchancements considered by Zhu et al. proportional to V(ud)/V(us). The measurement is part of a program of inelastic scattering measurements that were conducted by the G0 experiment, seeking to determine the N-Δ axial transition form factors using PV electron scattering.

Transverse beam spin asymmetries at backward angles in elastic electron-proton and quasielastic electron-deuteron scattering.

We have measured the beam-normal single-spin asymmetries in elastic scattering of transversely polarized electrons from the proton, and performed the first measurement in quasielastic scattering on the deuteron, at backward angles (lab scattering angle of 108°) for Q² = 0.22 GeV²/c² and 0.63 GeV²/c² at beam energies of 362 and 687 MeV, respectively. The asymmetry arises due to the imaginary part of the interference of the two-photon exchange amplitude with that of single-photon exchange. Results for the proton are consistent with a model calculation which includes inelastic intermediate hadronic (πN) states. An estimate of the beam-normal single-spin asymmetry for the scattering from the neutron is made using a quasistatic deuterium approximation, and is also in agreement with theory.

Missed opportunities for tuberculosis diagnosis.

BACKGROUND: In high tuberculosis (TB) burden, resource-poor countries, sputum smear microscopy remains the mainstay of diagnosis. The low sensitivity of this test means that patients with smear-negative but culture-positive TB pass undetected through the health care system. Such clinical episodes are missed opportunities for diagnosis and interruption of transmission, which might be averted through the application of more sensitive diagnostic tests. OBJECTIVES: To estimate the proportion of incident TB cases that might have been detected earlier than the actual date of diagnosis if a test more sensitive than smear microscopy had been used at an earlier presentation episode. METHOD: Retrospective cohort study in urban Peru, investigating health care facility interactions for symptoms suggestive of TB prior to TB diagnosis through patient interviews and a review of clinical records. RESULTS: Of 212 participants enrolled, 58% had one or more clinical interactions prior to their diagnostic episode. Of those with a prior episode, the median number of episodes was three. The median delay to diagnosis from first presentation was 26 days. CONCLUSION: There are clear missed opportunities for earlier TB diagnosis, delaying treatment initiation and continued spread of Mycobacterium tuberculosis to the community. The implementation of sensitive diagnostic tests appropriate to resource-poor settings should be given high priority.

Strange quark contributions to parity-violating asymmetries in the backward angle G0 electron scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton and quasielastic electron-deuteron scattering at Q2=0.22 and 0.63 GeV2. They are sensitive to strange quark contributions to currents in the nucleon and the nucleon axial-vector current. The results indicate strange quark contributions of approximately < 10% of the charge and magnetic nucleon form factors at these four-momentum transfers. We also present the first measurement of anapole moment effects in the axial-vector current at these four-momentum transfers.

ZNF397, a new class of interphase to early prophase-specific, SCAN-zinc-finger, mammalian centromere protein.

The centromere is a complex structure required for equal segregation of newly synthesised sister chromatids at mitosis. One of the significant objectives in centromere research is to determine the complete repertoire of protein components that constitute the kinetochore. Here, we identify a novel centromere protein using a centromere-positive autoimmune serum from a patient with watermelon stomach disease. Western blot and screening of a lambda phage expression library revealed a 60-kDa protein, ZNF397. This protein belongs to the classical Cys(2)His(2) group of the zinc-finger protein superfamily and contains two conserved domains: a leucine-rich SCAN domain and nine Cys(2)His(2) zinc fingers. Bioinformatic analysis shows that ZNF397 is conserved in placental mammals. Stable GFP:ZNF397-expressing human cells show co-localisation of ZNF397 with the constitutive centromere protein CENP-A during interphase and early prophase. Deletion and domain-swap constructs indicate that the SCAN domain is necessary but not sufficient for centromere localisation. Gene-knockout studies in mice using the mouse orthologue (Zfp397) reveal that ZNF397 is a non-essential protein. These properties define ZNF397 as a member of a new class of interphase to early prophase-specific and SCAN domain-containing mammalian centromere protein. The possible role of this protein in transcription at the centromere is discussed.

Transverse beam spin asymmetries in forward-angle elastic electron-proton scattering.

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely polarized 3 GeV electrons from unpolarized protons at Q2=0.15, 0.25 (GeV/c)2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A(n) provides a direct probe of the imaginary component of the 2gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.

Precision measurements of the nucleon strange form factors at Q2 approximately 0.1 GeV2.

We report new measurements of the parity-violating asymmetry A(PV) in elastic scattering of 3 GeV electrons off hydrogen and 4He targets with approximately 6.0 degrees . The 4He result is A(PV)=(+6.40+/-0.23(stat)+/-0.12(syst))x10(-6). The hydrogen result is A(PV)=(-1.58+/-0.12(stat)+/-0.04(syst))x10(-6). These results significantly improve constraints on the electric and magnetic strange form factors G(E)(s) and G(M)(s). We extract G(E)(s)=0.002+/-0.014+/-0.007 at =0.077 GeV2, and G(E)(s)+0.09G(M)(s)=0.007+/-0.011+/-0.006 at =0.109 GeV2, providing new limits on the role of strange quarks in the nucleon charge and magnetization distributions.

Gene gun-delivered pGM-CSF adjuvant induces enhanced emigration of two dendritic cell subsets from the skin.

Two subsets of sheep afferent lymph dendritic cells (DC) are defined by the differential expression of CD172a and CD45RA. The majority (~70%) of CD172a(+) subset is CD45RA/CD11c(+)/CD207(+)/TLR4(+). The CD172a(-) DC are CD45RA(+)/CD207(-) and express low levels of CD11c and CD86. Real-time RT-PCR showed that CD172(+) DC produce IL-1beta and IL-10 and high levels of IL-18 but almost no IL-12p40; CD172a(-) DC express IL-12p40 but no IL-10 and low levels of IL-1beta and IL-18. Gene gun-delivered granulocyte-macrophage colony-stimulating factor (pGM-CSF) caused an early rise in the output of CD172a(+) DC, changes to DC phenotype and significant increases in the levels of expression cytokine transcripts. However, pGM-CSF did not affect any qualitative changes to cytokine expression, CD172a(+) DC remained IL-10(+)/IL-12p40(-) and the CD172(-) DC remained IL-10(-)/IL-12p40(+).

Strange-quark contributions to parity-violating asymmetries in the forward g0 electron-proton scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.

Injection-related risk behaviors in young urban and suburban injection drug users in Chicago (1997-1999).

We compared injection-related risk practices between urban and suburban injection drug users (IDUs) in a large cross-sectional sample of young IDUs. From 1997 to 1999, we recruited 700 active IDUs aged 18 to 30 years in Chicago and its suburbs. A suburban residence was reported by 38% of participants. Participants were interviewed at four urban locations and screened for HIV and hepatitis C virus antibodies. Receptive sharing of syringes and other paraphernalia by urban and suburban IDUs in the preceding 6 months was compared using univariable and multivariable models. Sharing injection paraphernalia in the total sample was high, with 50% of participants reporting receptive syringe sharing and 70% reporting sharing cotton, cookers, and/or rinse water. After adjusting for demographic characteristics, injection settings, frequency, and duration of injection as well as ease of acquiring new syringes, suburban IDUs were significantly more likely than urban IDUs to share syringes (adjusted odds ratio = 1.7; 95% confidence interval: 1.1-2.5); however, the likelihood of sharing cotton, cookers, or rinse water was roughly equal. Despite overall higher risk profiles among suburban IDUs, HIV and hepatitis C prevalence levels were significantly lower than among urban participants. Current high levels of injection risk behaviors in suburban groups represent a potential for rapid dissemination of infection.

Circadian rhythmicity of cortisol and body temperature: morningness-eveningness effects.

The purpose of this study was to describe and compare the circadian rhythm of body temperature and cortisol, as well as self-reported clock times of sleep onset and offset on weekdays and weekends in 19 healthy adult "larks" (morning chronotypes) and "owls" (evening chronotypes), defined by the Home and Ostberg questionnaire. Day-active subjects entered the General Clinical Research Center, where blood was sampled every 2 h over 38 h for later analysis for cortisol concentration by enzyme immunoassay. Rectal body temperature was measured continuously. Lights were turned off at 22:30 for sleep and turned on at 06:00, when subjects were awakened. The acrophases (peak times) of the cortisol and temperature rhythms occurred 55 minutes (P < or = .05) and 68 minutes (P < .01), respectively, earlier in the morningness group. The amplitude of the cortisol rhythm was lower in the eveningness than in the morningness group (P = n.s.). Subject groups differed on all indices of habitual and preferred timing of sleep and work weekdays and weekends (P = .05-.001).

The impact of nalmefene on side effects due to intrathecal morphine at cesarean section.

Nalmefene is a long-acting opioid antagonist that provides long-term relief from side effects of intrathecal morphine sulfate. A randomized, double-blind, placebo-controlled study was conducted to determine whether prophylactic nalmefene could decrease side effects of intrathecal morphine given during cesarean section, without affecting analgesia. Sixty parturients were given 0.25 mg of intrathecal morphine, 12.5 micrograms of fentanyl, and 11.25 to 15 mg of bupivacaine. A dose of 0.25 microgram/kg of nalmefene or placebo was given by intravenous piggyback immediately after delivery of the neonate. Nausea, vomiting, pruritus, and level of sedation were assessed for a 24-hour period using a 4-point ordinal scoring system. Pain was assessed by using a 0- to 10-point verbal analogue scale. A 5-point analgesic satisfaction survey also was completed. Subjects who received nalmefene required supplemental analgesia at a median of 6.00 hours after intrathecal morphine, compared with 14.12 hours in the placebo group (P = .037). No differences were found between the groups in the incidence of pruritus, nausea and vomiting, level of sedation, or analgesic satisfaction. We concluded that nalmefene at a dose of 0.25 microgram/kg does not decrease the incidence of side effects but increases the need for supplemental analgesics.

Restorative effects of GDNF on striatal dopamine release in rats treated with neurotoxic doses of methamphetamine.

Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in striatal dopamine (DA) release and content. Glial cell line-derived neurotrophic factor (GDNF) has pronounced effects on dopaminergic systems in vivo, including neuroprotective effects against METH. The present experiments were designed to examine the ability of GDNF to reverse, or accelerate recovery from, METH-induced alterations in striatal DA release. Male Fischer-344 rats were administered METH (5 mg/kg, s.c.) or saline 4 times in one day at 2-hour intervals. Seven days later the animals were anesthetized and given a single injection of 10 microg GDNF, or vehicle, into the right striatum. Three weeks later microdialysis experiments were carried out in both the right and left striata to examine basal and evoked levels of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In animals treated with METH followed by vehicle 7 days later, there were significant reductions in potassium- and amphetamine-evoked overflow of DA, and in basal levels of DOPAC and HVA, compared to control animals. In rats treated with METH followed 7 days later with GDNF, there were significant increases in potassium- and amphetamine-evoked overflow of DA on the right, GDNF-treated, side of the brain compared to the left side. Basal levels of DOPAC and HVA were also elevated on the GDNF-treated side of the brain. These results suggest that GDNF can accelerate recovery of dopaminergic release processes in the striatum of rats treated with neurotoxic doses of METH.

Sleep impairments in healthy seniors: roles of stress, cortisol, and interleukin-1 beta.

STUDY OBJECTIVES: Increased stress responsivity and a longer-lasting glucocorticoid increase are common findings in aging studies. Increased cortisol levels at the circadian nadir also accompany aging. We used 24 h free urine cortisol to assess these age changes in healthy seniors. We hypothesized that free cortisol levels would explain individual differences in age-related sleep impairments. DESIGN: The study compared sleep, cortisol, and sleep-cortisol correlations under baseline and "stress" conditions in men and women. SETTING: Subjects were studied in the General Clinical Research Center under baseline conditions and a mildly stressful procedure (24 h indwelling intravenous catheter placement). PARTICIPANTS: Eighty-eight healthy, nonobese subjects (60 women and 28 men) from a large study of successful aging participated in the study. Mean ages were 70.6 (+/-6.2) and 72.3 (+/-5.7) years for women and men, respectively. MEASUREMENTS: The 24 h urines were collected for cortisol assay (radioimmunoassay [RIA]); blood was sampled at three diurnal time points for assay (enzyme-linked immunosorbent assay [ELISA]) of interleukin-1 (IL-1) beta; sleep architecture and sleep electroencephalograms (EEGs) were analyzed (after an adaptation and screening night) on baseline and stress nights via polysomnography and EEG power spectral analysis. RESULTS: Healthy older women and men with higher levels of free cortisol (24 h urine level) under a mild stress condition had impaired sleep (lower sleep efficiency; fewer minutes of stages 2, 3, and 4 sleep; more EEG beta activity during non-rapid eye movement sleep [NREM] sleep). Similar results were obtained when stress reactivity measures were used (cortisol and sleep values adjusted for baseline values), but not when baseline values alone were used. Gender differences were apparent: Men had higher levels of free urine cortisol in both baseline and mild stress conditions. Cortisol and sleep correlated most strongly in men; cortisol stress response levels explained 36% of the variance in NREM sleep stress responses. In women, but not men, higher cortisol was also associated with earlier time of arising and less REM sleep. Higher cortisol response to stress was associated with increased circulating levels of IL-1beta, explaining 24% of the variance in a subset of women. CONCLUSION: These results indicate that free cortisol (as indexed by 24 h urine values) can index responses to mild stress in healthy senior adults, revealing functional correlations (impaired sleep, earlier times of arising, more EEG beta activity during sleep, more IL-1beta) and gender differences.

Levels of methyleugenol in a subset of adults in the general U.S. population as determined by high resolution mass spectrometry.

We developed a sensitive and accurate analytical method for quantifying methyleugenol (ME) in human serum. Our method uses a simple solid-phase extraction followed by a highly specific analysis using isotope dilution gas chromatography-high resolution mass spectrometry. Our method is very accurate; its limit of detection is 3.1 pg/g and its average coefficient of variation is 14% over a 200-pg/g range. We applied this method to measure serum ME concentrations in adults in the general U.S. population. ME was detected in 98% of our samples, with a mean ME concentration of 24 pg/g (range < 3.1-390 pg/g). Lipid adjustment of the data did not alter the distribution. Bivariate and multivariate analyses using selected demographic variables showed only marginal relationships between race/ethnicity and sex/fasting status with serum ME concentrations. Although no demographic variable was a good predictor of ME exposure or dose, our data indicate prevalent exposure of U.S. adults to ME. Detailed pharmacokinetic studies are required to determine the relationship between ME intake and human serum ME concentrations.

Reliability and concurrent validity of DSM-IV subclinical symptom ratings for alcohol use disorders among adolescents.

BACKGROUND: The concurrent validity of subclinical ratings for psychiatric symptoms can help refine symptom definitions and threshold criteria. However, virtually no research has examined subclinical ratings for DSM-IV symptoms in psychiatric diagnostic interviews. This study examined the frequency, reliability, and concurrent validity of subclinical ratings for 11 symptoms of alcohol use disorders among adolescents. METHODS: Subjects were 239 male and 164 female adolescents ages 14 to 18 recruited from treatment and community sources. Symptoms and diagnoses were made with an adapted version of the Structured Clinical Interview for the DSM-IV. RESULTS: Subclinical ratings showed acceptable to high interrater reliability. The proportion of subclinical ratings tended to decrease with increasing levels of alcohol problems. For 10 of the 11 symptoms, subjects with subclinical ratings were distinguished from those with absent and/or those with present ratings. Subjects with subclinical ratings were often distinct from those with present ratings but less often distinct from those with absent ratings. CONCLUSIONS: For most of the DSM-IV alcohol use disorder symptoms, subclinical ratings appear to be reliable and valid and provide information beyond dichotomous symptom classifications for adolescents. Threshold criteria appear to be appropriate in many cases, but boundaries between absent and subclinical ratings are "fuzzy." Practical and research implications are discussed.