Prevalence of Violence Victimization and Perpetration Among Persons Aged 13-24 Years - Four Sub-Saharan African Countries, 2013-2015.

Violence is a major public health and human rights concern, claiming over 1.3 million lives globally each year (1). Despite the scope of this problem, population-based data on physical and sexual violence perpetration are scarce, particularly in low-income and middle-income countries (2,3). To better understand factors driving both children becoming victims of physical or sexual violence and subsequently (as adults) becoming perpetrators, CDC collaborated with four countries in sub-Saharan Africa (Malawi, Nigeria, Uganda, and Zambia) to conduct national household surveys of persons aged 13-24 years to measure experiences of violence victimization in childhood and subsequent perpetration of physical or sexual violence. Perpetration of physical or sexual violence was prevalent among both males and females, ranging among males from 29.5% in Nigeria to 51.5% in Malawi and among females from 15.3% in Zambia to 28.4% in Uganda. Experiencing physical, sexual, or emotional violence in childhood was the strongest predictor for perpetrating violence; a graded dose-response relationship emerged between the number of types of childhood violence experienced (i.e., physical, sexual, and emotional) and perpetration of violence. Efforts to prevent violence victimization need to begin early, requiring investment in the prevention of childhood violence and interventions to mitigate the negative effects of violence experienced by children.

Physicochemical and functional characteristics of lentil starch.

The physicochemical properties of lentil starch were measured and linked up with its functional properties and compared with those of corn and potato starches. The amylose content of lentil starch was the highest among these starches. The crystallinity and gelatinization enthalpy of lentil starch were the lowest among these starches. The high amylose: amylopectin ratio in lentil starch resulted into low crystallinity and gelatinization enthalpy. Gelatinization and pasting temperatures of lentil starch were in between those of corn and potato starches. Lentil starch gels showed the highest storage modulus, gel strength and pasting viscosity than corn and potato starch gels. Peleg's model was able to predict the stress relaxation data of these starches well (R(2)>0.98). The elastic modulus of lentil starch gel was less frequency dependent and higher in magnitude at high temperature (60 °C) than at lower temperature (10 °C). Lentil starch is suitable where higher gel strengthened pasting viscosity are desired.

Metabolic specialization of mouse embryonic stem cells.

Mouse embryonic stem (ES) cells are endowed with four unusual properties. They are exceedingly small, exhibiting an intracellular volume two to three orders of magnitude smaller than that of normal mammalian cells. Their rate of cell division, wherein cell doubling takes place in only 4-5 h, is more rapid than even the fastest growing cancer cell lines. They do not senesce. Finally, mouse ES cells retain pluripotency adequate to give rise to all cell types present in either gender of adult mice. We have investigated whether some or all of these unusual features might relate to the possibility that mouse ES cells exist in a specialized metabolic state. By evaluating the abundance of common metabolites as a function of the conversion of mouse ES cells into differentiated embryoid bodies, it was observed that the most radical changes in metabolite abundance related to cellular building blocks associated with one carbon metabolism. These observations led to the discovery that mouse ES cells use the threonine dehydrogenase (TDH) enzyme to convert threonine into acetyl-coenzyme A and glycine, thereby facilitating consumption of threonine as a metabolic fuel. Here we describe the results of a combination of nutritional and pharmacological studies, providing evidence that mouse ES cells are critically dependent on both threonine and the TDH enzyme for growth and viability.

A carbon dioxide, heat and chemical lure trap for the bedbug, Cimex lectularius.

A trap for the collection of bedbugs, Cimex lectularius Linnaeus (Hemiptera: Cimicidae), is described. The trap was baited with CO2 (50-400 mL/min), heat (37.2-42.2 degrees C) and a chemical lure comprised of 33.0 microg proprionic acid, 0.33 microg butyric acid, 0.33 microg valeric acid, 100 microg octenol and 100 microg L-lactic acid, impregnated into a gel. Laboratory studies, conducted in a square arena measuring 183 cm on each side, showed that traps with and without baits captured adult bedbugs, but traps with CO2 emissions of 50-400 mL/min caught significantly (P < 0.05) more bedbugs than traps without CO2. In an infested unoccupied apartment, traps with heat and with or without the chemical lure were tested without CO2 on 29 trap-days and with CO2 on 9 trap-days. The numbers of bedbugs captured were 656 and 5898 in traps without and with CO2, respectively. The numbers of bedbugs of all development stages captured were significantly greater in traps with CO2 (chi2 = 15 942, d.f. = 1, P < 10(-9)). A non-parametric two-way analysis of variance evaluation of six different traps with or without CO2, heat or a chemical lure monitored over 19 trap-days in an infested apartment showed that trap type was highly significant (n = 2833 bedbugs collected) (P < 10(-7)). The trap with CO2, heat and a chemical lure captured more bedbugs than the other traps, but only caught significantly more fourth and fifth instar nymphs than all other traps. Otherwise, the catches in this trap did not differ significantly from those caught by traps that contained CO2 and heat only. The total numbers of bedbugs collected for each trapping date (pooling all six traps) followed an exponential decline over the trapping period. This type of trap, which caught bedbugs in unoccupied apartments with and without furniture, and in an occupied apartment, may have utility in studying the ecology of bedbugs, in detecting bedbug infestations and in reducing numbers of bites by trapping host-seeking bedbugs.

The yeast metabolic cycle: insights into the life of a eukaryotic cell.

The budding yeast Saccharomyces cerevisiae undergoes robust oscillations in oxygen consumption during continuous growth under nutrient-limited conditions. Comprehensive microarray studies reveal that more than half of the yeast genome is expressed periodically as a function of these respiratory oscillations, thereby specifying an extensively orchestrated program responsible for regulating numerous cellular outputs. Here, we summarize the logic of the yeast metabolic cycle (YMC) and highlight additional cellular processes that are predicted to be compartmentalized in time. Certain principles of temporal orchestration as seen during the YMC might be conserved across other biological cycles.

Genetics and imaging to assess oocyte and preimplantation embryo health.

Two major criteria are currently used in human assisted reproductive technologies (ART) to evaluate oocyte and preimplantation embryo health: (1) rate of preimplantation embryonic development; and (2) overall morphology. A major gene that regulates the rate of preimplantation development is the preimplantation embryo development (Ped) gene, discovered in our laboratory. In mice, presence of the Ped gene product, Qa-2 protein, results in a fast rate of preimplantation embryonic development, compared with a slow rate of preimplantation embryonic development for embryos that are lacking Qa-2 protein. Moreover, mice that express Qa-2 protein have an overall reproductive advantage that extends beyond the preimplantation period, including higher survival to birth, higher birthweight, and higher survival to weaning. Data are presented that suggest that Qa-2 increases the rate of development of early embryos by acting as a cell-signalling molecule and that phosphatidylinositol-32 kinase is involved in the cell-signalling pathway. The most likely human homologue of Qa-2 has recently been identified as human leukocyte antigen (HLA)-G. Data are presented which show that HLA-G, like Qa-2, is located in lipid rafts, implying that HLA-G also acts as a signalling molecule. In order to better evaluate the second criterion used in ART (i.e. overall morphology), a unique and innovative imaging microscope has been constructed, the Keck 3-D fusion microscope (Keck 3DFM). The Keck 3DFM combines five different microscopic modes into a single platform, allowing multi-modal imaging of the specimen. One of the modes, the quadrature tomographic microscope (QTM), creates digital images of non-stained transparent cells by measuring changes in the index of refraction. Quadrature tomographic microscope images of oocytes and preimplantation mouse embryos are presented for the first time. The digital information from the QTM images should allow the number of cells in a preimplantation embryo to be counted non-invasively. The Keck 3DFM is also being used to assess mitochondrial distribution in mouse oocytes and embryos by using the k-means clustering algorithm. Both the number of cells in preimplantation embryos and mitochondrial distribution are related to oocyte and embryo health. New imaging data obtained from the Keck 3DFM, combined with genetic and biochemical approaches, have the promise of being able to distinguish healthy from unhealthy oocytes and embryos in a non-invasive manner. The goal is to apply the information from our mouse model system to the clinic in order to identify one and only one healthy embryo for transfer back to the mother undergoing an ART procedure. This approach has the potential to increase the success rate of ART and to decrease the high, and undesirable, multiple birth rate presently associated with ART.

McBindall--a better name for CCAAT/enhancer binding proteins?

C/EBP-related transcription factors regulate the balance between cell proliferation and mitotic growth arrest during terminal differentiation. Three new studies give evidence that this regulation is mediated by protein:protein interactions completely distinct from the role of C/EBPs in gene expression.

A conserved family of prolyl-4-hydroxylases that modify HIF.

Mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of HIF is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. We identified a conserved family of HIF prolyl hydoxylase (HPH) enzymes that appear to be responsible for this posttranslational modification. In cultured mammalian cells, inappropriate accumulation of HIF caused by forced expression of the HIF-1alpha subunit under normoxic conditions was attenuated by coexpression of HPH. Suppression of HPH in cultured Drosophila melanogaster cells by RNA interference resulted in elevated expression of a hypoxia-inducible gene (LDH, encoding lactate dehydrogenase) under normoxic conditions. These findings indicate that HPH is an essential component of the pathway through which cells sense oxygen.

NPAS2: an analog of clock operative in the mammalian forebrain.

Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain. NPAS2 is highly related in primary amino acid sequence to Clock, a transcription factor expressed in the suprachiasmatic nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To investigate the biological role of NPAS2, we prepared a neuroblastoma cell line capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified putative target genes by representational difference analysis, DNA microarrays, and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of the endogenous Per1, Per2, and Cry1 genes, which encode negatively activating components of the circadian regulatory apparatus, and repressed transcription of the endogenous BMAL1 gene. Analysis of the frontal cortex of wild-type mice kept in a 24-hour light-dark cycle revealed that Per1, Per2, and Cry1 mRNA levels were elevated during darkness and reduced during light, whereas BMAL1 mRNA displayed the opposite pattern. In situ hybridization assays of mice kept in constant darkness revealed that Per2 mRNA abundance did not oscillate as a function of the circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of a molecular clock operative in the mammalian forebrain.

Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors.

Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle. Although built to fluctuate at or near a 24-hour cycle, the clock can be entrained by light, activity, or food. Here we show that the DNA-binding activity of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers is regulated by the redox state of nicotinamide adenine dinucleotide (NAD) cofactors in a purified system. The reduced forms of the redox cofactors, NAD(H) and NADP(H), strongly enhance DNA binding of the Clock:BMAL1 and NPAS2:BMAL1 heterodimers, whereas the oxidized forms inhibit. These observations raise the possibility that food, neuronal activity, or both may entrain the circadian clock by direct modulation of cellular redox state.

PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine kinase.

PAS domains regulate the function of many intracellular signaling pathways in response to both extrinsic and intrinsic stimuli. PAS domain-regulated histidine kinases are common in prokaryotes and control a wide range of fundamental physiological processes. Similarly regulated kinases are rare in eukaryotes and are to date completely absent in mammals. PAS kinase (PASK) is an evolutionarily conserved gene product present in yeast, flies, and mammals. The amino acid sequence of PASK specifies two PAS domains followed by a canonical serine/threonine kinase domain, indicating that it might represent the first mammalian PAS-regulated protein kinase. We present evidence that the activity of PASK is regulated by two mechanisms. Autophosphorylation at two threonine residues located within the activation loop significantly increases catalytic activity. We further demonstrate that the N-terminal PAS domain is a cis regulator of PASK catalytic activity. When the PAS domain-containing region is removed, enzyme activity is significantly increased, and supplementation of the purified PAS-A domain in trans selectively inhibits PASK catalytic activity. These studies define a eukaryotic signaling pathway suitable for studies of PAS domains in a purified in vitro setting.

Does early hospital discharge with home support of families with preterm infants affect breastfeeding success? A randomized trial.

UNLABELLED: The aim of the present study was to determine if earlier discharge of preterm infants (<37 wk) from hospital is safe and if it affects breastfeeding rates. In a pilot observational study, premature infants received full oral (sucking) feeds for a mean (SD) 7.7 +/- 7.9 d before discharge. In the main study, 308 preterm infants were randomly assigned to either Early Discharge (148 infants) when fully orally fed but not yet gaining weight or Routine Discharge (160 infants) when fully orally fed and also gaining weight before discharge. A further 122 mothers declined randomization. The Early Discharge group was followed by Visiting Nurse Specialists who were available 24 h a day, while the Routine group was followed by the Home Care Nurses available on week days. There were no significant differences between the groups in birthweight or gestational age. The Early Discharge group were discharged 2.5 +/- 2 d after full oral feeding compared to 4.4 +/- 2.7 d for the Routine group (p < 0.001) and 6.1 +/- 5 d for those who declined. However, there was no significant difference between the Early and Routine groups for breastfeeding either at discharge (80 vs 83%), or 6 wk (55 vs 60%) or 6 mo after discharge (36 vs 36%), or for weight gain, or rates of re-hospitalization (8.8% vs 11.9% at 6 wk, p = 0.37). CONCLUSION: Early discharge from hospital once a preterm infant can take full oral feeds does not alter later breastfeeding rates when adequate visiting nursing support is available.

A double bootstrap method to analyze linear models with autoregressive error terms.

A new method for the analysis of linear models that have autoregressive errors is proposed. The approach is not only relevant in the behavioral sciences for analyzing small-sample time-series intervention models, but it is also appropriate for a wide class of small-sample linear model problems in which there is interest in inferential statements regarding all regression parameters and autoregressive parameters in the model. The methodology includes a double application of bootstrap procedures. The 1st application is used to obtain bias-adjusted estimates of the autoregressive parameters. The 2nd application is used to estimate the standard errors of the parameter estimates. Theoretical and Monte Carlo results are presented to demonstrate asymptotic and small-sample properties of the method; examples that illustrate advantages of the new approach over established time-series methods are described.

Impaired cued and contextual memory in NPAS2-deficient mice.

Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PAS domain transcription factor expressed in multiple regions of the vertebrate brain. Targeted insertion of a beta-galactosidase reporter gene (lacZ) resulted in the production of an NPAS2-lacZ fusion protein and an altered form of NPAS2 lacking the bHLH domain. The neuroanatomical expression pattern of NPAS2-lacZ was temporally and spatially coincident with formation of the mature frontal association/limbic forebrain pathway. NPAS2-deficient mice were subjected to a series of behavioral tests and were found to exhibit deficits in the long-term memory arm of the cued and contextual fear task. Thus, NPAS2 may serve a dedicated regulatory role in the acquisition of specific types of memory.

The Pseudomonas quinolone signal regulates rhl quorum sensing in Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa uses intercellular signals to control the density-dependent expression of many virulence factors. The las and rhl quorum-sensing systems function, respectively, through the autoinducers N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone (C(4)-HSL), which are known to positively regulate the transcription of the elastase-encoding gene, lasB. Recently, we reported that a second type of intercellular signal is involved in lasB induction. This signal was identified as 2-heptyl-3-hydroxy-4-quinolone and designated the Pseudomonas quinolone signal (PQS). PQS was determined to be part of the quorum-sensing hierarchy since its production and bioactivity depended on the las and rhl quorum-sensing systems, respectively. In order to define the role of PQS in the P. aeruginosa quorum-sensing cascade, lacZ gene fusions were used to determine the effect of PQS on the transcription of the quorum-sensing system genes lasR, lasI, rhlR, and rhlI. We found that in P. aeruginosa, PQS caused a major induction of rhlI'-lacZ and had lesser effects on the transcription of lasR'-lacZ and rhlR'-lacZ. We also observed that the transcription of both rhlI'-lacZ and lasB'-lacZ was cooperatively effected by C(4)-HSL and PQS. Additionally, we present data indicating that PQS was not produced maximally until cultures reached the late stationary phase of growth. Taken together, our results imply that PQS acts as a link between the las and rhl quorum-sensing systems and that this signal is not involved in sensing cell density.

Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa.

Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa, which contains two quorum sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB, which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones.

The role of alcohol dehydrogenase in the metabolism of the colon carcinogen methylazoxymethanol.

The aim of this study was to determine whether the cytosolic enzyme alcohol dehydrogenase (ADH) activates methylazoxymethanol (MAM) in the mouse colon and whether differential tumor susceptibility in the mouse is dependent, in part, on strain-related differences in MAM metabolism by ADH. Liver and colon cytosols were isolated from 7-week-old male tumor-susceptible (SWR/J) and -resistant (AKR/J) mice. Minimal reduction of NAD+ was found in colon cytosols from AKR/J mice at the highest concentration (2 mM) of MAM tested. In liver cytosols, only SWR was capable of sustaining NAD+ reduction with MAM, although at very low levels. Despite minimal reactivity with MAM, however, mouse cytosols did effectively reduce NAD+ in the presence of the common ADH subrates ethanol and benzyl alcohol. NAD(+)-coupled oxidation of benzyl alcohol was significantly higher (two- to three-fold, p < 0.05) in mouse colon cytosols compared to activity present within corresponding rat tissues. Incubation of colon and liver cytosols with the ADH-3 inhibitor 4-methylpyrazole markedly (95-100% of controls) reduced ethanol oxidation in both strains. However, 4-methylpyrazole was a less effective inhibitor of benzyl alcohol oxidation in AKR/J colons, suggesting a different ADH isoform complement. An opposite inhibition pattern of benzyl alcohol oxidation was seen in the liver, where 4-methylpyrazole produced a greater inhibition in SWR/J mice. These studies suggest that the metabolism of the proximate mutagen MAM occurs by processes in the mouse that are independent of ADH.

Outcomes in abdominal hysterectomy patients with benign disease. Use of physician-developed clinical protocols.

OBJECTIVE: To develop a clinical protocol for standardizing preoperative and postoperative care in abdominal hysterectomy patients with benign disease while maintaining quality and increasing efficiency. STUDY DESIGN: Protocol and nonprotocol groups of patients were compared with respect to key quality and efficiency outcomes in a non-randomized study. Patient group outcomes were compared using descriptive, Student's t, chi 2 and log-rank statistics. Statistical tests were performed at a .05 level of significance. RESULTS: Results from two separate protocol study periods conducted in 1996 and 1997 are reported. In both study periods statistical analyses and graphic presentations illustrate that protocol implementation improved quality of care by increasing the percentage of patients receiving appropriate antibiotic prophylaxis; maintained quality as monitored through 30-day readmission rates and a postdischarge patient survey; and improved efficiency, as evidenced by shorter times to incision and length of hospital stay. CONCLUSION: At Toledo Hospital, the clinical practice protocol directed at abdominal hysterectomy patients has been an effective tool in efforts to improve quality and efficiency in patient care.

The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development.

Mice lacking the hypoxia-inducible transcription factor EPAS1 die at mid-gestation. Despite normal morphological development of the circulatory system, EPAS1-deficient mice display pronounced bradycardia. In addition to the vascular endothelium, EPAS1 is expressed intensively in the organ of Zuckerkandl (OZ), the principle source of catecholamine production in mammalian embryos. EPAS1-deficient embryos contained substantially reduced catecholamine levels. Mid-gestational lethality was rescued by administration of the catecholamine precursor DOPS to pregnant females. We hypothesize that EPAS1 expressed in the OZ senses hypoxia during mid-gestational development and translates this signal into an altered pattern of gene expression, leading to increases in circulating catecholamine levels and proper cardiac function.