Assessing bioavailability of ruminally protected methionine and lysine prototypes.

Met and Lys are essential AA that can limit lactational performance in dairy cattle fed protein-sufficient diets. Thus, there is industry demand for ruminally protected (RP) sources of Met and Lys. One method of providing ruminal protection for Met and Lys is lipid encapsulation. The objective of this work was to assess 3 lipid-encapsulated Met prototypes (P1, P2, and P3) and 1 Lys prototype (P4) to determine ruminal protection, small intestine absorption (experiment 1), and animal production responses (experiment 2). Ruminal protection was estimated from 8-h in situ retention during ruminal incubation and intestinal absorption from plasma appearance after an abomasal bolus of the in situ retentate. Blood samples were collected over time to determine plasma Met and Lys concentration responses compared with unprotected Lys and Met infused abomasally. The prototypes were not exposed to the total diet or subjected to typical feed handling methods before evaluation. The bioavailability of P1, P2, and P3 Met prototypes was found to be 14, 21, and 18% of the initial AA material, respectively. The RP-Lys prototype had a bioavailability of 45%. To evaluate production responses, 20 Holstein cows were randomly assigned to 2 trials (n = 10 each) in a replicated Latin square design with 14-d periods. The base diet was predicted to be deficient in metabolizable Met (-14.8 g/d) and Lys (-16.1 g/d) per the Cornell Net Carbohydrate and Protein System (version 6.55). In the Met trial, the base diet was supplemented with RP-Lys to meet Lys requirements, and treatments were as follows: no added RP-Met (NCM), NCM plus Smartamine M (SM; Adisseo, Alpharetta, GA), and NCM plus P1, P2, or P3 at 148% of the Met content of SM. In the Lys trial, the base diet was supplemented with RP-Met to meet the Met requirement, and treatments were as follows: no added Lys (NCL), NCL plus AjiProL (AL; Ajinomoto Heartland Inc., Chicago, IL), and NCL plus P4 at 55, 78, or 102% of the reported absorbed Lys in AL. All products were top dressed on the diet without prior mixing or extended exposure to the rest of the diet. Milk protein concentration significantly increased when diets were supplemented with P2, P3, or SM (3.12, 3.12, and 3.11%, respectively) compared with NCM (3.02%). Only P1 (3.04%) was significantly lower than SM. Prototype P2 had the greatest numerical milk protein output response among the 3 RP-Met prototypes, suggesting that it may have had the greatest efficacy when supplemented into these rations. There was a numerical milk protein concentration response to AL and a linear increase in milk protein concentration for P4. The P4 and AL treatments resulted in comparable milk protein production regardless of P4 dose.

Comparing embodiment experiences in expert meditators and non-meditators using the rubber hand illusion.

One assessment of embodiment is the rubber hand illusion (RHI), a visuo-tactile illusion in which individuals attribute a sense of ownership to a rubber hand and disownership to their real hand. Interestingly, interoception seems to influence RHI susceptibility. In this study, we administered the RHI and the Multidimensional Assessment of Interoceptive Awareness (MAIA) to examine embodiment experiences and interoceptive awareness in experienced meditators (n = 15) and non-meditators (n = 15). We found that meditators reported less intensity in rubber hand ownership, but there was no significant difference between groups with respect to disownership of their real hand or drift in finger proprioception. Moreover, we found, from our MAIA results, that disownership experiences were associated with a feeling of trusting one's body in non-meditators and with the ability to maintain attention to unpleasant bodily sensations in meditators. These results suggest a unique relationship between interoceptive awareness and embodiment related to meditation.

Geography of the circadian gene clock and photoperiodic response in western North American populations of the three-spined stickleback Gasterosteus aculeatus.

Controlled laboratory experiments were used to show that Oregon and Alaskan three-spined stickleback Gasterosteus aculeatus, collected from locations differing by 18° of latitude, exhibited no significant variation in length of the polyglutamine domain of the clock protein or in photoperiodic response within or between latitudes despite the fact that male and female G. aculeatus are photoperiodic at both latitudes. Hence, caution is urged when interpreting variation in the polyglutamine repeat (PolyQ) domain of the gene clock in the context of seasonal activities or in relationship to photoperiodism along geographical gradients.

Long-term increases in young-of-the-year growth of Arctic cisco Coregonus autumnalis and environmental influences.

Arctic cisco Coregonus autumnalis young-of-year (YOY) growth was used as a proxy to examine the long-term response of a high-latitude fish population to changing climate from 1978 to 2004. YOY growth increased over time (r² = 0·29) and was correlated with monthly averages of the Arctic oscillation index, air temperature, east wind speed, sea-ice concentration and river discharge with and without time lags. Overall, the most prevalent correlates to YOY growth were sea-ice concentration lagged 1 year (significant correlations in 7 months; r² = 0·14-0·31) and Mackenzie River discharge lagged 2 years (significant correlations in 8 months; r² = 0·13-0·50). The results suggest that decreased sea-ice concentrations and increased river discharge fuel primary production and that life cycles of prey species linking increased primary production to fish growth are responsible for the time lag. Oceanographic studies also suggest that sea ice concentration and fluvial inputs from the Mackenzie River are key factors influencing productivity in the Beaufort Sea. Future research should assess the possible mechanism relating sea ice concentration and river discharge to productivity at upper trophic levels.

Nestling Physiology Is Independent of Somatic Development in a Common Raptor, the American Kestrel (Falco sparverius).

AbstractAlthough many studies have documented the developmental trajectory of somatic traits in birds, few measure physiological traits, and even fewer document individual variation in developmental trajectory across ecological context. Hematological traits underlying aerobic capacity can be predictive of nestling survival, fledgling flight ability, and ultimately recruitment. This study aimed to assess individual variation in the developmental trajectory of two physiological traits that underlie aerobic capacity, hematocrit and hemoglobin concentration, in relation to somatic development and ecological context. Our study species, the American kestrel (Falco sparverius), is sexually dimorphic and therefore likely to show sexual variation in developmental trajectory and nestling maturity. We used lay date, year, brood size, nestling sex ratio, and parental nest visit rate to assess ecological context. Although somatic traits showed similar trajectories across nestlings, developmental trajectory for hematocrit and hemoglobin concentration showed individual variation not previously documented. This individual variation in developmental change, or trajectory, for physiological traits could not be explained by somatic development, sex, parental nest visit rate, lay date, year, brood size, or nestling sex ratio. However, we did find higher final hemoglobin concentration in 2018 and in nests with earlier lay dates. These findings demonstrate the importance of assessing physiological traits that capture aspects of individual quality distinct from somatic traits. Future studies are needed to understand the causes of individual variation in developmental trajectory, which cannot be explained by the ecological variables presented here, and the potential fitness consequences of this variation.

Visualization, characterization, and turnover of CD8+ memory T cells in virus-infected hosts.

The cellular basis of T cell memory is a controversial issue and progress has been hampered by the inability to induce and to trace long-term memory T cells specific for a defined antigen in vivo. By using the murine model of lymphocytic choriomeningitis virus (LCMV) infection and an adoptive transfer system with CD8+ T cells from transgenic mice expressing an LCMV-specific T cell receptor, a population of authentic memory T cells specific for LCMV was generated and analyzed in vivo. The transgenic T cells that have expanded (1,000-fold) and then decreased (10-fold) in LCMV-infected C57BL/6 recipient mice exhibited the following characteristics: they were (a) of larger average cell size than their naive counterparts but smaller than day 8 effector cells; (b) heterogeneous with respect to expression of cell surface "memory" markers; and (c) directly cytolytic when isolated from recipient spleens. The time-dependent proliferative activity of these LCMV-specific memory T cells was analyzed in the recipients by bromodeoxyuridine labeling experiments in vivo. The experiments revealed that LCMV-specific CD8+ memory T cells can persist in LCMV-immune mice for extended periods of time (>2 mo) in the absence of cell division; the memory population as a whole survived beyond 11 mo.

Fish growth rates and lake sulphate explain variation in mercury levels in ninespine stickleback (Pungitius pungitius) on the Arctic Coastal Plain of Alaska.

Mercury concentrations in freshwater food webs are governed by complex biogeochemical and ecological interactions that spatially vary and are often mediated by climate. The Arctic Coastal Plain of Alaska (ACP) is a heterogeneous, lake-rich landscape where variability in mercury accumulation is poorly understood. Earlier research indicated that the level of catchment influence on lakes varied spatially on the ACP, and affected mercury accumulation in lake sediments. This work sought to determine drivers of spatial variation in mercury accumulation in lake food webs on the ACP. Three lakes that were a priori identified as "high catchment influence" (Reindeer Camp region) and three lakes that were a priori identified as "low catchment influence" (Atqasuk region) were sampled, and variability in water chemistry, food web ecology, and mercury accumulation was investigated. Among-lake differences in ninespine stickleback (Pungitius pungitius) length-adjusted methylmercury concentrations were significantly explained by sulphate concentration in lake water, a tracer of catchment runoff input. This effect was mediated by fish growth, which had no pattern between regions. Together, lake water sulphate concentration and fish age-at-size (proxy for growth) accounted for nearly all of the among-lake variability in length-adjusted methylmercury concentrations in stickleback (R2adj = 0.94, p < 0.01). The percentage of total mercury as methylmercury (a proxy for net Hg methylation) was higher in sediments of more autochthonous, "low catchment influence" lakes (p < 0.05), and in the periphyton of more allochthonous, "high catchment influence" lakes (p < 0.05). The results indicate that dominant sources of primary production (littoral macrophyte/biofilm vs. pelagic phytoplankton) and food web structure (detrital vs. grazing) are regulated by catchment characteristics on the ACP, and that this ultimately influences the amount of methylmercury in the aquatic food web. These results have important implications for predicting future mercury concentrations in fish in lakes where fish growth rates and catchment inputs may change in response to a changing climate.

Patterns of violence and coercion with mental health among female and male trafficking survivors: a latent class analysis with mixture models.

AIMS: Human trafficking is a crime and a human rights violation that involves various and simultaneous traumatic events (sexual and physical violence, coercion). Yet, it is unknown how the patterning of violence and coercion affects the mental health of female and male trafficking survivors. METHODS: We conducted a cross-sectional study using a sample of 1015 female and male survivors of trafficking who received post-trafficking assistance services in Cambodia, Thailand or Vietnam. We assessed symptoms of anxiety and depression with the Hopkins Symptoms Checklist and symptoms of post-traumatic stress disorder (PTSD) with the Harvard Trauma Questionnaire. Violence was measured with questions from the World Health Organization International Study on Women's Health. Latent class analysis (LCA) was used to identify distinct patterns of violence and coercion in females and males. Novel multi-step mixture modelling techniques were employed to assess the association of the emergent classes with anxiety, depression and PTSD in females and males. RESULTS: LCA identified two distinct classes of violence and coercion experiences in females (class I: severe sexual and physical violence and coercion (20%); class II: sexual violence and coercion (80%)) and males (class I: severe physical violence and coercion (41%); class II: personal coercion (59%)). Females in class I had a two-fold increase in the odds of anxiety (OR = 2.10; 95% CI: 1.57-2.81) and PTSD (OR = 2.07; 95% CI: 1.03-4.17) compared with females in class II, but differences in the prevalence of anxiety, depression and PTSD were not significant when comparing males in class I to class II. CONCLUSIONS: Specific patterns of violence and coercion provide a more in-depth understanding of the role of gender in the experience of violence and coercion and its association with mental health in survivors of trafficking. This information could be useful to target comprehensive mental health services for female and male trafficking survivors.

Educación alimentaria en pacientes en dialisis / Nutritional education in dialysis patients

La enfermedad renal crónica terminal aumenta el riesgo cardiovascular y puede ocasionar defectos en la mineralización ósea. Para prevenir esto, se debe mantener el fósforo plasmático normal, que depende de la diálisis, los quelantes y la ingesta de fósforo, principalmente de origen inorgánico, incorporado mediante aditivos alimentarios. Las intervenciones nutricionales son pilares en el tratamiento de estos pacientes. El objetivo es facilitar estrategias alimentarias a un grupo de pacientes pediátricos en diálisis, mediante educación alimentaria nutricional, para aumentar el consumo de alimentos naturales, disminuyendo la ingesta de fósforo inorgánico especialmente de los productos cárnicos procesados. Materiales y métodos: se estudió una población pediátrica en diálisis. Se preparó un programa educativo con atención personalizada, instrucción alimentaria y seguimiento mensual, seguido de un taller. Resultados: n: 17 pacientes, edad decimal media de 12,3, 53% sexo masculino, 88% en hemodiálisis. Previo a la intervención el 64,7% consumía productos cárnicos procesados. Luego del taller el 58,8% disminuyó su consumo, el 41,2% aumentó la ingesta de preparaciones caseras, el 53% incorporó nuevos condimentos, de los cuales el 89% presentó al incorporarlos, mejor aceptación a las preparaciones. Conclusiones: la hiperfosfatemia está presente en alrededor del 50% de los pacientes en diálisis asociándose a un incremento entre 20% al 40% del riesgo de mortalidad. La presencia de fósforo oculto en los alimentos y la falta de adherencia hacen prioritario trabajar en programas educativos que favorezcan el aprendizaje colaborativo, centralizados en prácticas culinarias, para brindar herramientas que faciliten una alimentación natural, disminuyendo el consumo de ultraprocesados (AU)

Chronic end-stage renal disease increases the risk of cardiovascular disease and may lead to defects in bone mineralization. In order to prevent these risks, normal plasma phosphorus levels should be maintained. Achieving this goal depends on dialysis, chelators, and phosphorus intake, mainly of inorganic origin, incorporated through food supplements. Nutritional interventions are crucial in the treatment of these patients. The objective is to facilitate nutritional strategies to a group of pediatric dialysis patients, through food education, to increase the consumption of natural foods, decreasing the intake of inorganic phosphorus, especially from processed meat products. Materials and methods: a pediatric population undergoing dialysis was studied. An educational program was prepared with personalized care, nutritional instruction, and monthly follow-up visits, followed by a workshop. Results: n: 17 patients, mean age 12.3 years, 53% male, 88% on hemodialysis. Prior to the intervention, 64.7% consumed processed meat products. After the workshop, 58.8% decreased their consumption, 41.2% increased the intake of homemade food, 53% incorporated new seasonings, of whom 89% reported better acceptance of the preparations when they were incorporated. Conclusions: hyperphosphatemia is observed in around 50% of patients undergoing dialysis and is associated with a 20% to 40% increased risk of mortality. The presence of hidden phosphorus in food and the lack of adherence point to the need for the development of educational programs that promote collaborative learning, focusing on food-preparation practices. These programs should provide tools that facilitate a natural diet, reducing the consumption of ultra-processed food (AU)

Isolation and physical characterization of three essential conidiation genes from Aspergillus nidulans.

We cloned and characterized three genes from Aspergillus nidulans, designated brlA, abaA, and wetA, whose activities are required to complete different stages of conidiophore development. Inactivation of these genes causes major abnormalities in conidiophore morphology and prevents expression of many unrelated, developmentally regulated genes, without affecting the expression of nonregulated genes. The three genes code for poly(A)+ RNAs that begin to accumulate at different times during conidiation. The brlA- and abaA-encoded RNAs accumulate specifically in cells of the conidiophore. The wetA-encoded RNA accumulates in mature conidia. Inactivation of the brlA gene prevents expression of the abaA and wetA genes, whereas inactivation of the abaA gene prevents expression of the wetA gene. Our results confirm genetic predictions as to the temporal and spatial patterns of expression of these genes and demonstrate that these patterns are specified at the level of RNA accumulation.

Transcription profiles of the bacterium Mycoplasma pneumoniae grown at different temperatures.

Applying microarray technology, we have investigated the transcriptome of the small bacterium Mycoplasma pneumoniae grown at three different temperature conditions: 32, 37 and 32 degrees C followed by a heat shock for 15 min at 43 degrees C, before isolating the RNA. From 688 proposed open-reading frames, 676 were investigated and 564 were found to be expressed (P < 0.001; 606 with P < 0.01) and at least 33 (P < 0.001; 77 at P < 0.01) regulated. By quantitative real-time PCR of selected mRNA species, the expression data could be linked to absolute molecule numbers. We found M.pneumoniae to be regulated at the transcriptional level. Forty-seven genes were found to be significantly up-regulated after heat shock (P < 0.01). Among those were the conserved heat shock genes like dnaK, lonA and clpB, but also several genes coding for ribosomal proteins and 10 genes of unassigned functions. In addition, 30 genes were found to be down-regulated under the applied heat shock conditions. Further more, we have compared different methods of cDNA synthesis (random hexamer versus gene-specific primers, different RNA concentrations) and various normalization strategies of the raw microarray data.

Methotrexate accumulates to similar levels in animals transplanted with normal versus drug-resistant transgenic marrow.

Gene transfer and expression of methotrexate (MTX)-resistant variants of dihydrofolate reductase (DHFR) in normal hematopoietic cells is a potential strategy to permit administration of larger doses of MTX by alleviating drug toxicity in normal cells and tissues that are drug sensitive. We have previously demonstrated that transplantation of marrow from transgenic mice expressing drug-resistant DHFRs conferred upon normal recipient animals resistance to MTX at levels that are usually toxic for hematopoietic and gastrointestinal (GI) tissues. One explanation for the observed protection from GI toxicity by drug-resistant marrow is that MTX could be cleared more rapidly in animals maintaining a more healthy hematopoietic system. To evaluate this possibility, we carried out MTX pharmacokinetic studies in mice that received transplanted transgenic marrow expressing either of two different DHFR variants, administering increasing doses of MTX up to 4 mg/kg/day. Animals received i.p. injection precisely every 24 h. Every 4 days, three animals from each group were sacrificed, and their plasma and intestines were assayed for MTX. Animals transplanted with transgenic Arg-22 DHFR drug-resistant marrow maintained hematocrit levels that were about 4-fold higher at 3 weeks after transplant than those of untreated animals or animals that received normal marrow cells. Animals that received normal marrow did not survive beyond 25 days and did not accumulate higher levels of MTX than animals that received a transgenic marrow transplant. Untreated animals exhibited a higher rate of survival (36 days) but again did not accumulate higher levels of MTX than the transgenic marrow recipients. When the experiment was repeated using transgenic Tyr-22 DHFR marrow, the levels of MTX in the plasma or GI tissues did not differ significantly between groups. Intestinal concentrations of MTX in both experiments were about 4-5-fold higher than those in the plasma. These results indicate that protection from MTX toxicity conferred by expression of drug-resistant DHFR activity in the marrow is not the result of a higher rate of MTX clearance from the circulation in comparison with control animals but a true resistance of hematopoietic and GI tissues to MTX. The maintenance of antifolate levels in animals protected from MTX toxicity implies that this procedure should not compromise the antitumor efficacy of MTX.

Quantitation of urinary metabolites of a tobacco-specific lung carcinogen after smoking cessation.

We quantified urinary levels of two metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in people who had stopped smoking: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide, 4-[(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). Twenty-seven people completed the study. Thirteen used the nicotine patch starting at the quit date, whereas the others used no patch. Two 24-h urine samples were collected on 2 consecutive days before smoking cessation; blood was also obtained. Beginning at their quit date, subjects provided 24-h urine samples on days 7, 21, 42, 70, 98, and 126, and some subjects also provided samples at later times. The urine was analyzed for NNAL, NNAL-Gluc, nicotine plus nicotine-N-glucuronide, and cotinine plus cotinine-N-glucuronide. Some blood samples were also analyzed for NNAL. The decline of urinary NNAL and NNAL-Gluc after smoking cessation was much slower than expected. This was clearly demonstrated by comparison with cotinine and nicotine levels in urine. One week after smoking cessation, 34.5% of baseline NNAL plus NNAL-Gluc was detected in urine, whereas the corresponding values for cotinine and nicotine were 1.1 and 0.5%, respectively. Even 6 weeks after cessation, 7.6% of the original levels of NNAL plus NNAL-Gluc remained. In some subjects, NNAL plus NNAL-Gluc were detected 281 days after cessation. The distribution half-life for NNAL and NNAL-Gluc was 3-4 days, whereas the elimination half-life was 40-45 days. Total body clearance of NNAL was estimated to be 61.4 +/- 35.4 ml/min, and volume of distribution in the beta-phase was estimated to be 3800 +/- 2100 liters, indicating substantial distribution into the tissues. Parallel studies in rats treated chronically or acutely with NNK in the drinking water support the conclusion that NNAL has a large volume of distribution. There was no effect of the nicotine patch on levels of NNAL plus NNAL-Gluc, indicating that NNK is not formed endogenously from nicotine. The results of this study demonstrate that NNAL and NNAL-Gluc are slowly cleared from the body after smoking cessation, indicating the presence of a high-affinity compartment where NNK, NNAL, and/or NNAL-Gluc are retained or sequestered and slowly released.

Chemoprevention of pulmonary carcinogenesis by aerosolized budesonide in female A/J mice.

This investigation is part of a continuing effort to develop effective chemoprevention for carcinogenesis of the lung. The present study explores the use of aerosol administrations for this purpose. The agent selected for initial study was the synthetic glucocorticoid budesonide. This selection was based on previous work in which budesonide added to the diet was found to inhibit pulmonary adenoma formation in female A/J mice. However, high dose levels were required, i.e., of the order of 300 microg/kg, of body weight [L. W. Wattenberg and R. D. Estensen, Carcinogenesis (Lond.), 18: 2015-2017, 1997]. For aerosol administration of budesonide, a nose-only technique has been developed that entails nebulization of the compound dissolved in ethanol and subsequent stripping off of the solvent (less than 3 microl ethanol/liter of air remaining at the site of inhalation). The budesonide particles produced by the apparatus had a mass median aerodynamic diameter of less than 1 microm. An experiment has been carried out in which the inhibitory effects of aerosolized budesonide, given for 1 min six times a week, were studied. Concentrations of budesonide of 26, 81, and 148 microg/liter of air (calculated doses of 23, 72, and 126 microg/kg of body weight) were used. The aerosols were started 1 week after three oral administrations of benzo(a)pyrene (2 mg/20 g of body weight) to female A/J mice. All three doses of budesonide resulted in more than 80% inhibition of pulmonary tumor formation compared to the aerosol control and 90% or greater compared to mice not exposed to aerosol. The difference in inhibition is due to the aerosol procedure itself, which produces a reduction in tumor formation. A decrease in splenic weight (evidence of a systemic effect) occurred at all doses of budesonide. To the best of our knowledge, this is the first published effort at the use of aerosol administration to prevent neoplasia of the respiratory tract. The results of the present study show that administration of a potential chemopreventive agent by aerosol at a low dose can inhibit the occurrence of pulmonary carcinogenesis in female A/J mice.

Regulation of E2F4 mitogenic activity during terminal differentiation by its heterodimerization partners for nuclear translocation.

E2F/DP heterodimers play a pivotal role in the regulation of cell growth and differentiation. A decrease in E2F/DP activity occurs during cell cycle arrest and differentiation. However, very little is known about the specific role of the various E2F/DP members along the transition from proliferation to terminal differentiation. We have previously shown that E2F4 accounts for the vast majority of the endogenous E2F in differentiating muscle cells. Here, we show that E2F4, which lacks a nuclear localization signal (nls), is distributed in both the nucleus and the cytoplasm, in either asynchronously growing myoblasts or differentiated myotubes. E2F4 nuclear accumulation is induced by the binding in the cytoplasm with specific partners p107, pRb2/p130, and DP3delta, an nls-containing spliced form of DP3, which provide the nls. Although overexpression of E2F4/DP3delta reactivates the cell cycle in quiescent cells, the E2F4 nuclear accumulation induced by pRb2/p130 and p107 correlates with cell growth arrest Moreover, E2F4/DP3delta-induced cell cycle reactivation is efficiently counteracted by either p107 or pRb2/p130 overexpression. Reinduction in quiescent cells of DNA synthesis by E2F1/DP1 overexpression is abrogated by coexpression of pRb and is hampered by MyoD overexpression. Both pRb2/p130 and pRb, as well as MyoD, are up-regulated in myotubes. Accordingly, multinucleated myotubes, which are induced to reenter the S-phase by oncoviral proteins, are refractory to cell cycle reactivation by forced expression of E2F4/DP3delta or E2F1/DP1. Thus, E2F/DP repression represents only one of multiple redundant circuits that control the postmitotic state in terminally differentiated cells and that are targeted by adenovirus E1A and SV40 large T antigen.

Prevalence and risk of violence and the mental, physical and sexual health problems associated with human trafficking: an updated systematic review.

BACKGROUND: To update and expand on a 2012 systematic review of the prevalence and risk of violence and the prevalence and risk of physical, mental and sexual health problems among trafficked people. METHOD: Systematic review and meta-analysis. Searches of 15 electronic databases of peer-reviewed articles and doctoral theses were supplemented by reference screening, citation tracking of included articles and expert recommendations. Studies were included if they reported on the prevalence or risk of violence while trafficked, or the prevalence or risk of physical, mental or sexual health outcomes among people who have been trafficked. Two reviewers independently screened papers for eligibility and appraised the quality of included studies. RESULTS: Thirty-seven papers reporting on 31 studies were identified. The majority of studies were conducted in low and middle-income countries with women and girls trafficked into the sex industry. There is limited but emerging evidence on the health of trafficked men and the health consequences of trafficking into different forms of exploitation. Studies indicate that trafficked women, men and children experience high levels of violence and report significant levels of physical health symptoms, including headaches, stomach pain and back pain. Most commonly reported mental health problems include depression, anxiety and post-traumatic stress disorder. Although serological data on sexually transmitted infections are limited, women and girls trafficked for sexual exploitation self-report symptoms suggestive of a high prevalence of infections. Limitations of the review include methodological weaknesses of primary studies and some differences in definition and operationalisation of trafficking, which hinder comparability and generalisability of the results. CONCLUSIONS: There is increasing evidence human trafficking is associated with high prevalence and increased risk of violence and a range of physical and mental health problems. Although more studies have emerged in recent years reporting on the health of trafficked men and people trafficked for forms of exploitation other than in the sex industry, further research is needed in this area. Appropriate interventions and support services to address the multiple and serious medical needs, especially mental health, of trafficked people are urgently needed.

Comparison of risk stratification tools in predicting outcomes of patients with higher-risk myelodysplastic syndromes treated with azanucleosides.

Established prognostic tools in patients with myelodysplastic syndromes (MDS) were largely derived from untreated patient cohorts. Although azanucleosides are standard therapies for higher-risk (HR)-MDS, the relative prognostic performance of existing prognostic tools among patients with HR-MDS receiving azanucleoside therapy is unknown. In the MDS Clinical Research Consortium database, we compared the prognostic utility of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Prognostic Scoring System (MDAPSS), World Health Organization-based Prognostic Scoring System (WPSS) and the French Prognostic Scoring System (FPSS) among 632 patients who presented with HR-MDS and were treated with azanucleosides as the first-line therapy. Median follow-up from diagnosis was 15.7 months. No prognostic tool predicted the probability of achieving an objective response. Nonetheless, all five tools were associated with overall survival (OS, P=0.025 for the IPSS, P=0.011 for WPSS and P<0.001 for the other three tools). The corrected Akaike Information Criteria, which were used to compare OS with the different prognostic scoring systems as covariates (lower is better) were 4138 (MDAPSS), 4156 (FPSS), 4196 (IPSS-R), 4186 (WPSS) and 4196 (IPSS). Patients in the highest-risk groups of the prognostic tools had a median OS from diagnosis of 11-16 months and should be considered for up-front transplantation or experimental approaches.

Intracoronary stenting compared with conventional therapy for abrupt vessel closure complicating coronary angioplasty: a matched case-control study.

OBJECTIVES: A case-control analysis was performed to compare clinical outcome after intracoronary stenting with that after conventional therapy for abrupt vessel closure. BACKGROUND: Previous studies have demonstrated that stenting after abrupt vessel closure results in marked angiographic improvement and preservation of coronary flow, leading to the anticipation of similar improvement in clinical outcome. METHODS: Sixty-one of 92 consecutive patients treated at two clinical sites by intracoronary stenting for abrupt vessel closure were matched, according to angiographic features of closure and estimated left ventricular mass threatened by ischemia, with patients treated conventionally during the 18 months before stent availability. In 33 pairs of matched patients, vessel closure was established; in 28 pairs, it was threatened (coronary dissection or worsening stenosis with preservation of normal anterograde flow). Baseline clinical and angiographic characteristics were comparable in the two matched groups. Patients with indeterminate mechanisms of total occlusion (31%) or dissections < 15 mm long (43%) predominated; patients with visible thrombus (8%) or dissections > 15 mm long (18%) were infrequently represented. Stents were successfully deployed in 60 of 61 patients at a median of 52 min (range 3 to 269) after the onset of closure. RESULTS: When compared with conventional treatment, stenting resulted in less residual stenosis (26% vs. 49% diameter stenosis, p < 0.001), a greater likelihood of restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow (97% vs. 72%, p < 0.001) and a reduction in the need for emergency bypass surgery (4.9% vs. 18%, p = 0.02). However, the incidence of Q wave myocardial infarction was nearly the same in the two groups (32% vs. 20%, respectively, p = NS). In the group with stenting, peak creatine kinase level and the frequency of Q wave infarction after established vessel closure increased with the time to stent placement (p = 0.001 and 0.054, respectively); the incidence of procedure-related Q wave infarction in patients who underwent stenting within 45 min of closure was very low (3.9%). In-hospital death occurred in 3.3% of patients in each treatment group. At a mean of 6.3 months of follow-up after hospital discharge, survival free from late cardiac death, myocardial infarction, bypass surgery or coronary angioplasty was 74.9% and 81.3% in the stent and the control treatment group, respectively (p = NS). CONCLUSIONS: Although early treatment of established vessel closure by intracoronary stenting was associated with a low incidence of both myocardial infarction and emergency bypass surgery, the likelihood or severity of infarction was not reduced among those in whom stents were implanted later. Patients with threatened vessel closure could not be shown to benefit from stent treatment. These data provide preliminary indications for stent placement in the acute period to be validated in larger randomized studies.

Thrombosis of a flexible coil coronary stent: frequency, predictors and clinical outcome.

OBJECTIVES: The aim of this study was to evaluate the predictors and clinical sequelae of stent thrombosis. BACKGROUND: Although coronary artery stenting is being increasingly applied, the major unique complication of stent thrombosis is not well characterized. METHODS: We studied 145 patients who underwent coronary artery stenting with the Gianturco-Roubin flexible coil design for abrupt vessel closure or to prevent restenosis. There were 17 stented vessel closures (11.7%), 7 as a result of acute (< 24 h) and 10 of subacute (days 1 to 21) thrombosis. RESULTS: In seven patients successful coronary recanalization was achieved with thrombolytic agents and balloon angioplasty. Creatine kinase was significantly elevated in 13 patients, with a Q wave myocardial infarction in 11 and emergency coronary artery bypass grafting in 8. Comparisons (multivariate analysis) with a control cohort (n = 33) of patients without thrombosis matched for age, gender and vessel stented revealed lesion eccentricity (p = 0.003), unstable angina (p = 0.048) and indication for stent implantation (abrupt closure versus restenosis) (p = 0.002), as predictors of thrombotic occlusion of stented vessels. Subtherapeutic anticoagulation (activated partial thromboplastin time < 2 times control value, prothrombin time < 1.4 control value) occurred at least once during the hospital stay in all 10 patients with subacute thrombosis and in 20 of 33 control patients (p = 0.047). In 2 patients with subacute thrombosis and 11 control subjects, subtherapeutic anticoagulation was necessitated by bleeding. CONCLUSIONS: Early thrombosis after coronary stenting was relatively common (> 10%), occurring predominantly in eccentric lesions and in patients with unstable angina pectoris. This complication is associated with significant adverse clinical outcomes and may be reduced by more intensive anticoagulation yet, in a delicate balance, can be precipitated by inadequate heparin therapy.