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Introduction: Adolescence is a crucial stage of physical and sexual maturation and development and a period in which understanding sexual and reproductive health (SRH) is important. SRH interventions and toolkits provide a range of valuable resources and information to young people, educators, and members of the community on numerous topics, including contraception and puberty., Objectives: The usefulness and reliability of these available toolkits have not been previously studied, thus limiting our understanding of their appropriateness and contents. Hence, this scoping review aimed to synthesize the available toolkits aimed at the SRH of adolescents and young adults to understand the contents, design, and information gaps., Methods: A systematic search was conducted of 6 medical databases and 12 gray literature sites. Sixteen toolkits published globally before May 2023 were included in our review., Results: The majority of toolkits (n = 12) contained information related to general SRH knowledge and contraception, whereas only 3 contained information on teenage pregnancy. We found that aiming the toolkits toward educators and health care workers was a favorable design over targeting adolescents and young adults directly and that vulnerable youth-including LGBTQI+ (lesbian, gay, bisexual, transgender, queer or questioning, asexual or allied, intersex, and additional identities) and youth from humanitarian settings-were not well represented., Conclusion: We identified key gaps in the inclusion of information in a range of SRH topics, such as LGBTQI+ sexuality, teenage pregnancy, and safe abortion, in the currently available SRH toolkits and their lack of applicability in a global context. Furthermore, we provide recommendations for areas of improvement to encourage adolescents' agency in their SRH education., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Recent advancements in shRNA and Cas protein technologies have enabled functional screening methods targeting genes or non-coding regions using single or pooled shRNA and sgRNA. CRISPR-based systems have also been developed for modulating DNA accessibility, resulting in CRISPR-mediated interference (CRISPRi) or activation (CRISPRa) of targeted genes or genomic DNA elements. However, there is still a lack of software tools for integrating diverse array of functional genomics screening outputs that could offer a cohesive framework for comprehensive data integration. Here, we developed PitViper, a flexible and interactive open-source software designed to fill this gap, providing reliable results for the type of elements being screened. It is an end-to-end automated and reproducible bioinformatics pipeline integrating gold-standard methods for functional screening analysis. Our sensitivity analyses demonstrate that PitViper is a useful tool for identifying potential super-enhancer liabilities in a leukemia cell line through genome-wide CRISPRi-based screening. It offers a robust, flexible, and interactive solution for integrating data analysis and reanalysis from functional screening methods, making it a valuable resource for researchers in the field., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Background: Little is known about human papillomavirus (HPV) vaccination among immigrant children in Canada. We conducted a study in Alberta, Canada to assess HPV vaccine coverage among school-aged immigrant children compared with non-immigrant children., Methods: This cohort study analysed population-based linked administrative health data to measure HPV vaccine coverage for 346 749 school-aged children, including 31 656 immigrants. Coverage was examined at 12 y of age from 2008 to 2018 for females, and from 2014 to 2018 for males and both sexes combined; vaccine series completion was considered receipt of three doses, with initiation (one or more dose) as a supplementary analysis. Multivariable logistic regression examined the association of vaccine coverage with migration status, adjusting for sociodemographic variables., Results: Between 2014 and 2018, HPV vaccination coverage among immigrant children at age 12 y was significantly higher (52.58%) compared with non-immigrant children (47.41%). After controlling for place of residence, income quintile, biological sex and year, immigrant children had 1.10 greater odds (95% confidence interval 1.07 to 1.14) of receiving three doses of HPV vaccine compared with non-immigrant children. Immigrants from Asia and Africa had the highest coverage (60.25-68.78%), while immigrants from North America, Oceania and South America had the lowest coverage (39.97-48.36%)., Conclusions: It is encouraging that immigrant children had higher HPV vaccine coverage compared with non-immigrants. Among immigrants, routine immunization promotion strategies should be tailored based on the country of origin., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Acquired demyelinating syndrome associated with myelin oligodendrocyte glycoprotein antibodies, named recently myelin oligodendrocyte glycoprotein-associated disease, represents >27% of this paediatric syndrome. Relapses occur in 40% of them, which may be associated with severe outcomes. Aiming to identify biomarker allowing to predict relapse, we measured both myelin oligodendrocyte glycoprotein antibodies and neurofilament light chain levels in blood samples of patients that are known to reflect axonal injuries in neurological diseases including demyelinating autoimmune disorders. Three groups of patients were selected: relapsing myelin oligodendrocyte glycoprotein-associated disease ( n = 8), non-relapsing myelin oligodendrocyte glycoprotein-associated disease ( n = 7) and control patients with non-inflammatory neurological diseases ( n = 12). Neurofilament light chain concentrations were measured in plasma of these three groups of patients using the high-sensitivity single-molecule array method at onset of the disease and 6 months later. At onset of the disease, we found that levels of neurofilament light chain in blood of non-relapsing patients were significantly higher than in control patients (means: 98.36 ± 22.66 versus 12.47 ± 2.47 pg/mL, ** P < 0.01, Kruskal-Wallis test). The mean neurofilament light chain value in relapsing patients (82.16 ± 38.41 pg/mL) was not significantly different from that in non-relapsing and in control patients. Plasma myelin oligodendrocyte glycoprotein antibody levels were 2.5-fold higher in relapsing than in non-relapsing patients without reaching significance (means: 15.26 ± 4.87 versus 5.96 ± 1.13; two-tailed Mann-Whitney U-test P = 0.119). Plasma neurofilament light chain correlated significantly with myelin oligodendrocyte glycoprotein antibody levels in relapsing (two-tailed Spearman r = 0.8, P = 0.0218) but not in non-relapsing (two-tailed Spearman r = 0.17, P = 0.71). Interestingly, the ratio of neurofilament light chain-to-myelin oligodendrocyte glycoprotein antibodies was significantly lower in relapsing than in non-relapsing patients (means: 5.19 ± 1.61 versus 21.87 ± 6.13; two-tailed Mann-Whitney U-test P = 0.014). These findings suggest that measuring both neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels in patients at onset of demyelinating disease could predict relapse of myelin oligodendrocyte glycoprotein-associated disease., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Teenage pregnancies carry an increased risk of adverse obstetric and health outcomes for mothers and children., Methods: This study assessed the prevalence and predictors of teenage pregnancies over time in Pakistan using the Pakistan Demographic and Health Survey (PDHS). Data on 400 076 ever-married pregnant women aged 15-49 y from four PDHS datasets were used. Teenage pregnancy was the outcome variable, whereas a woman's and her partner's education, occupation, wealth quintile, region, place of residence and access to knowledge on family planning were the explanatory variables. Pooled prevalence was estimated and regression analysis was undertaken to produce an adjusted prevalence ratio with 95% CIs., Results: Although the prevalence of teenage pregnancy decreased from 54.4% in 1990-1991 to 43.7% in 2017-2018, the pooled prevalence was 42.5% (95% CI 37.9 to 49.6%). The prevalence of teenage pregnancy was significantly associated with place of residence, wealth quintile, education and occupation., Conclusion: Despite a growing focus on women's education, access to sexual and reproductive health (SRH) services and contraception in the last decade in Pakistan, the prevalence of teenage pregnancy is still high. There is a pressing need to develop appropriate strategies for increasing access to education, SRH services and use of contraception in Pakistan., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

We compared candidemia due to Candida auris and other non-C.auris cases in hospitalized COVID-19 patients over a period of 9 months at our institution. Candidemia cases in all admitted patients (with or without COVID-19) from April to December 2020 were identified. Electronic records were accessed to record clinical data of COVID-19 patients with candidemia. For statistical analysis, independent samples Mann-Whitney U test was used for continuous and Fisher's exact test was used for categorical variables.A total of 26 candidemia cases (four C.auris, 22 non-C.auris) in 2438 admitted COVID-19 (10.7 per 1000 admissions) and 59 candidemia cases (six C.auris, 53 non-C.auris) in admitted non-COVID patients (8.2 per 1000 admission) were identified. The proportion of C.auris candidemia in COVID-19 and non-COVID-19 patients was 15.4 and 10%, respectively. 4/26 of COVID-19 candidemia patients were aged ≤ 15 years (10 months--15 years). Comparison of C.auris and non-C. auris candidemia cases reveal significant difference in prior antifungal exposure, present in 100% C. auris candidemia versus 27% non-C. auris candidemia patients (P-value 0.014). Although not statistically significant, C. auris candidemia patients had a longer stay in hospital before candidemia (20 vs. 9 days), higher isolation rate of multidrug resistant bacteria (100 vs. 50%), increased rate of prior colonization of Candida species (50 vs. 14%) and lower mean beta-d-glucan levels (48.73 pg/ml vs. 138.146 pg/ml). Both C. auris and non-C. auris COVID-19 patients had similar mortality rate (67 vs. 65%). A significant number of critically ill COVID-19 patients developed candidemia in our study highlighting the need for prompt diagnosis and management., Lay Summary: 26 candidemia cases (4 Candida auris;22 non-C. auris) in COVID-19 patients (April-December 2020) are reported from Pakistan. Compared to non-C. auris, C. auris candidemia patients had higher prior antifungal exposure, longer hospital stay, higher rates of MDR bacteria and Candida colonization., (© The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area., Methods: We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area., Results: In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at <30 days. Among the 203 surviving patients following the acute phase, long-term follow-up (median 180 days) was available for 189 (93%) patients. Major adverse events occurred in 30 (16%) patients during follow-up, including 12 deaths (6%) after a median of 78 days from onset of symptoms. Overall, cardiovascular events, infections and gastrointestinal bleeding were the main major adverse events. Post-COVID-19 cachexia was observed in 25/189 (13%) patients. Lower initial albuminaemia was significantly associated with this cachexia. No reinfection with severe acute respiratory syndrome coronavirus 2 was observed., Conclusions: This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of tumor necrosis factor inhibitor (TNFi), comparing monoclonal anti-TNF antibodies to the soluble TNF receptor. We used B cell activating factor belonging to the TNF family (BAFF)-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month-old BAFF-Tg mice were treated with TNFi for 12 months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at euthanasia. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF antibodies compared to both controls and mice treated with the soluble TNF receptor, even at a high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF antibodies. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF antibodies increase the risk of lymphoma in B cell-driven autoimmunity. These data suggest a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF antibodies., (© 2021 British Society for Immunology.)

May Measurement Month (MMM) is an annual global blood pressure (BP) screening campaign aimed at obtaining standardized BP measurements and other relevant health information from members of the community to increase awareness of elevated BP and the associated risks. Adults (≥18 years) were recruited through opportunistic sampling across the various Australian states during May 2019. Three BP readings were recorded in a standardized manner for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic BP ≥140 mmHg, or a diastolic BP ≥90 mmHg (according to the MMM protocol) or taking antihypertensive medication. Multiple imputation was used to estimate participants' mean BP where three readings were not available. Of the 2877 participants, 901 (31.3%) had hypertension of whom 455 (50.5%) were aware of their condition, and 366 (40.6%) were on antihypertensive medication. Of those taking antihypertensive medication, 54.3% were controlled to <140/90 mmHg with the remaining 45.7% of participants inadequately treated. Approximately 74% of treated patients were on a single antihypertensive medication. The MMM campaign provides an important platform for standardized compilation of BP data and creation of BP awareness in Australia and other nations worldwide. Data from the 2019 MMM campaign highlight that BP control rates in Australia remain unacceptably low., (Published on behalf of the European Society of Cardiology. © The Author(s) 2021.)

Background: Maintenance or improvement of physical function is an important treatment target in the management of patients with axial spondyloarthritis (axSpA); measurement tools that can detect changes in physical function are therefore important., Objectives: The objective of this study was to compare responsiveness and interpretability of the patient-reported Bath Ankylosing Spondylitis Functional Index (BASFI) and the Ankylosing Spondylitis Performed-Based Improvement (ASPI) in measuring change in physical function after exercise in patients with axSpA., Design: This was a sub-study of 58 patients nested within a randomized controlled trial comparing the effect of 12 weeks of exercise with usual care., Methods: Responsiveness and interpretability were assessed according to the Consensus-based Standards for the selection of health status Measurement Instrument. Responsiveness was assessed by testing 8 predefined hypotheses for ASPI and BASFI. Interpretability was assessed by: (1) using patients' reported change as an anchor ("a little better" = minimal important change) and (2) by categorizing patients with a 20% improvement as responders., Results: For ASPI and BASFI, 5 of 8 (63%) versus 2 of 8 (25%) of the predefined hypotheses for responsiveness were confirmed. The minimal important change values for improvement in physical function were 3.7 seconds in ASPI and 0.8 points (on a scale from 0 to 10) for BASFI. In the intervention group, 21 of 30 (70%) and 13 of 30 (43%) of the patients were categorized as responders measured with ASPI and BASFI, respectively. There was a tendency towards a floor effect in BASFI, as 8 of 58 (14%) patients scored the lowest value at baseline., Limitations: This study was limited by its moderate sample size., Conclusions: Our findings suggest that ASPI is preferable over BASFI when evaluating physical function after exercise interventions in patients with axSpA., (© 2020 American Physical Therapy Association.)

Background: In the high-prevalence setting of Pakistan, screening, diagnosis and treatment services for chronic hepatitis C (CHC) patients are commonly offered in specialized facilities. We aimed to describe the cascade of care in a Médecins Sans Frontières primary health care clinic offering CHC care in an informal settlement in Karachi, Pakistan., Methods: This was a retrospective cohort analysis using routinely collected data. Three different screening algorithms were assessed among patients with one or more CHC risk factors., Results: Among the 87 348 patients attending the outpatient clinic, 5003 (6%) presented with one or more risk factors. Rapid diagnostic test (RDT) positivity was 38% overall. Approximately 60% of the CHC patients across all risk categories were in the early stage of the disease, with an aspartate aminotransferase:platelet ratio index score <1. The sequential delays in the cascade differed between the three groups, with the interval between screening and treatment initiation being the shortest in the cohort tested with GeneXpert onsite., Conclusions: Delays between screening and treatment can be reduced by putting in place more patient-centric testing algorithms. New strategies, to better identify and treat the hidden at-risk populations, should be developed and implemented., (© The Author(s) 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Introduction: The present study investigated the associations between smoking, pain, and opioid consumption in the 3 months after major surgery in patients seen by the Transitional Pain Service. Current smoking status and lifetime pack-years were expected to be related to higher pain intensity, more opioid use, and poorer opioid weaning after surgery., Methods: A total of 239 patients reported smoking status in their presurgical assessment (62 smokers, 92 past smokers, and 85 never smokers). Pain and daily opioid use were assessed in hospital before postsurgical discharge, at first outpatient visit (median of 1 month postsurgery), and at last outpatient visit (median of 3 months postsurgery). Pain was measured using numeric rating scale. Morphine equivalent daily opioid doses were calculated for each patient., Results: Current smokers reported significantly higher pain intensity (p < .05) at 1 month postsurgery than never smokers and past smokers. Decline in opioid consumption differed significantly by smoking status, with both current and past smokers reporting a less than expected decline in daily opioid consumption (p < .05) at 3 months. Decline in opioid consumption was also related to pack-years, with those reporting higher pack-years having a less than expected decline in daily opioid consumption at 3 months (p < .05)., Conclusions: Smoking status may be an important modifiable risk factor for pain intensity and opioid use after surgery., Implications: In a population with complex postsurgical pain, smoking was associated with greater pain intensity at 1 month after major surgery and less opioid weaning 3 months after surgery. Smoking may be an important modifiable risk factor for pain intensity and opioid use after surgery.

Lyme disease is an emerging public health threat in Canada. In this context, rapid detection of new risk areas is essential for timely application of prevention and control measures. In Canada, information on Lyme disease risk is collected through three surveillance activities: active tick surveillance, passive tick surveillance, and reported human cases. However, each method has shortcomings that limit its ability to rapidly and reliably identify new risk areas. We investigated the relationships between risk signals provided by human cases, passive and active tick surveillance to assess the performance of tick surveillance for early detection of emerging risk areas. We used regression models to investigate the relationships between the reported human cases, Ixodes scapularis (Say; Acari: Ixodidae) ticks collected on humans through passive surveillance and the density of nymphs collected by active surveillance from 2009 to 2014 in the province of Quebec. We then developed new risk indicators and validated their ability to discriminate risk levels used by provincial public health authorities. While there was a significant positive relationship between the risk signals provided all three surveillance methods, the strongest association was between passive tick surveillance and reported human cases. Passive tick submissions were a reasonable indicator of the abundance of ticks in the environment (sensitivity and specificity [Se and Sp] < 0.70), but were a much better indicator of municipalities with more than three human cases reported over 5 yr (Se = 0.88; Sp = 0.90). These results suggest that passive tick surveillance provides a timely and reliable signal of emerging risk areas for Lyme disease in Canada.

Objective: Ketoconazole (KTZ) is one of few available treatments for Cushing's syndrome (CS). Although KTZ has been associated with severe hepatotoxicity, little information is available about hepatic safety in CS. The aim of this study was to document changes in liver function in patients with CS treated with KTZ., Design: An observational prospective French cohort study (Compassionate Use Programme (CUP))., Methods: Enrolled patients were stratified into a KTZ-naive cohort and a cohort already treated by another formulation of ketoconazole (KTZ-switch cohort). Liver function markers (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, γ-glutamyltransferase and bilirubin) were monitored at regular intervals. Patients with ALT > 3 × ULN (upper limit of normal), total bilirubin > 2 × ULN or both ALP > 2 × ULN and ALT > ULN were considered to have liver injury., Results: Overall, 108 patients were analysed (47 KTZ-naïve; 61 KTZ-switch). The median KTZ dose was 600 mg/day. Most abnormalities observed were asymptomatic mild increases of liver enzymes. Four patients in the KTZ-naïve cohort (8.5%) and two in the KTZ-switch cohort (3.3%) developed liver injury, considered related to KTZ in three cases (all KTZ-naïve in the first month of treatment). Five patients had mild liver function abnormalities at baseline and two had proven liver metastases. Two patients recovered on discontinuation of KTZ and the remaining patient died of unrelated causes., Conclusions: These findings highlight the need for close monitoring of liver enzymes especially during the first six months of treatment. Liver enzyme abnormalities usually occurred within four weeks were asymptomatic and could be reversed on timely discontinuation of KTZ., (© 2018 European Society of Endocrinology.)

In this study, we identified a new Bacillus strain isolated from an Algerian salty lake that produces metabolites that are active against Gram-positive and Gram-negative bacteria, as well as fungal pathogens. The draft genome sequence of the strain is presented herein. Genome sequence analysis identified the strain to be B. amyloliquefaciens subspecies plantarum F11, and showed that the strain carries the gene clusters for the production of a number of bioactive and surface-active compounds. These include the lipopeptides surfactin and fengycin, antibacterial polyketides macrolactin and bacillaene, and a putative novel lanthipeptide, among others. Through an activity-guided purification method using hydrophobic interaction chromatographic techniques, we confirmed the ability of the strain to produce fengycin lipopeptides. The identities of the isolated fengycin homologs were ascertained through tandem mass spectrometry., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Heart transplantation (HT) and ventricular assist devices (VAD) for the management of end-stage heart failure have not been directly compared. We compare the outcomes and use of resources with these 2 strategies in 2 European countries with different allocation systems., Methods: We studied 83 patients managed by VAD as the first option in Bad Oeynhausen, Germany (Group I) and 141 managed with either HT or medical therapy, as the first option, in Paris, France (Group II). The primary end-point was 2-year survival. Kaplan-Meier analyses were performed after the application of propensity score weights to mitigate the effects of non-random group assignment. The secondary end-points were resource utilization and costs. Subgroup analyses were performed for patients undergoing HT and patients treated with inotropes at the enrolment time., Results: The Group I patients were more severely ill and haemodynamically compromised, and 28% subsequently underwent HT vs 55% primary HT in Group II, P < 0.001. The adjusted probability of survival was 44% in Group I vs 70% in Group II, P <0.0001. The mean cumulated 2-year costs were €281 361 ± 156 223 in Group I and €47 638 ± 35 061 in Group II, P < 0.0001. Among patients who underwent HT, the adjusted probability of survival in Group I (n = 23) versus Group II (n = 78) was 76% versus 68%, respectively (0.09), though it differed in the inotrope-treated subgroups (77% in Group I vs 67% in Group II, P = 0.04)., Conclusions: HT should remain the first option for end-stage heart failure patients, associated with improved outcomes and better cost-effectiveness profile. VAD devices represent an option when transplant is not possible or when patient presentation is not optimal., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The development and maintenance of the zones of the adrenal cortex and their steroidal output are extremely important in the control of gluconeogenesis, the stress response, and blood volume. Sonic Hedgehog (Shh) is expressed in the adrenal cortex and signals to capsular cells, which can respond by migrating into the cortex and converting into a steroidogenic phenotype. Delta-like homologue 1 (Dlk1), a member of the Notch/Delta/Serrate family of epidermal growth factor-like repeat-containing proteins, has a well-established role in inhibiting adipocyte differentiation. We demonstrate that Shh and Dlk1 are coexpressed in the outer undifferentiated zone of the male rat adrenal and that Dlk1 signals to the adrenal capsule, activating glioma-associated oncogene homolog 1 transcription in a β1 integrin- and Erk1/2-dependent fashion. Moreover, Shh and Dlk1 expression inversely correlates with the size of the zona glomerulosa in rats after manipulation of the renin-angiotensin system, suggesting a role in the homeostatic maintenance of the gland.

Aims: Cardiac surgery and coronary angiography are both associated with risk of acute kidney injury (AKI). We hypothesized that the risk of post-operative AKI increases when coronary angiogram and cardiac surgery are performed in close succession, without sufficient time for recovery from the adverse effects of intravenous contrast., Methods and Results: We included 2133 consecutive patients who underwent cardiac surgery at the Minneapolis Veterans Administration Medical Center from 2004 to 2010. Acute kidney injury was defined by the AKI network and the risk, injury, failure, loss, end-stage (RIFLE) criteria. Patients were 66 ± 10 years old. Mean pre-operative creatinine and estimated glomerular filtration rate were 1.1 ± 0.4 mg/dL and 75 ± 22 mL/min/1.73 m(2), respectively. Cardiac surgery was performed 14 days (range 0-235) after coronary angiography. Acute kidney injury occurred in 680 (32%) patients per AKI network, 390 (18%) patients per RIFLE risk, and 111 (5%) patients per RIFLE injury criteria. Age, body mass index, diabetes mellitus, New York Heart Association class III/IV, cardiopulmonary bypass time, and impaired pre-operative renal function were independent predictors of AKI. However, time between coronary angiogram and cardiac surgery was not a predictor (P = 0.41). AKI occurred in 35% of 433 patients operated within 3 days of coronary angiogram vs. 31% of 1700 patients operated after 3 days (P = 0.17). Results were the same in patients with impaired pre-operative renal function and those with contrast-induced nephropathy., Conclusion: Risk of AKI after cardiac surgery is not influenced by the time between coronary angiogram and cardiac surgery. These results do not support the notion of delaying cardiac surgery for the sole purpose of renal recovery after coronary angiogram.

Human genetic diseases have been successfully corrected by integration of functional copies of the defective genes into human cells, but in some cases integration of therapeutic vectors has activated proto-oncogenes and contributed to leukemia. For this reason, extensive efforts have focused on analyzing integration site populations from patient samples, but the most commonly used methods for recovering newly integrated DNA suffer from severe recovery biases. Here, we show that a new method based on phage Mu transposition in vitro allows convenient and consistent recovery of integration site sequences in a form that can be analyzed directly using DNA barcoding and pyrosequencing. The method also allows simple estimation of the relative abundance of gene-modified cells from human gene therapy subjects, which has previously been lacking but is crucial for detecting expansion of cell clones that may be a prelude to adverse events.

The present study enlightens the role of the antagonistic potential of nonpathogenic strain B21 against sulfate-reducing bacteria (SRB) consortium. The inhibitor effects of strain B21 were compared with those of the chemical biocide tetrakishydroxymethylphosphonium sulfate (THPS), generally used in the petroleum industry. The biological inhibitor exhibited much better and effective performance. Growth of SRB in coculture with bacteria strain B21 antagonist exhibited decline in SRB growth, reduction in production of sulfides, with consumption of sulfate. The observed effect seems more important in comparison with the effect caused by the tested biocide (THPS). Strain B21, a dominant facultative aerobic species, has salt growth requirement always above 5% (w/v) salts with optimal concentration of 10-15%. Phylogenetic analysis based on partial 16S rRNA gene sequences showed that strain B21 is a member of the genus Bacillus, being most closely related to Bacillus qingdaonensis DQ115802 (94.0% sequence similarity), Bacillus aidingensis DQ504377 (94.0%), and Bacillus salarius AY667494 (92.2%). Comparative analysis of partial 16S rRNA gene sequence data plus physiological, biochemical, and phenotypic features of the novel isolate and related species of Bacillus indicated that strain B21 may represent a novel species within the genus Bacillus, named Bacillus sp. (EMBL, FR671419). The results of this study indicate the application potential of Bacillus strain B21 as a biocontrol agent to fight corrosion in the oil industry.

The physiological performance of durum wheat and two related amphiploids was studied during the reproductive stage under different combinations of salinity and irrigation. One triticale, one tritordeum, and four durum wheat genotypes were grown in pots in the absence of stress until heading, when six different treatments were imposed progressively. Treatments resulted from the combination of two irrigation regimes (100% and 35% of container water capacity) with three levels of water salinity (1.8, 12, and 17 dS m(-1)), and were maintained for nearly 3 weeks. Gas exchange and chlorophyll fluorescence and content were measured prior to harvest; afterwards shoot biomass and height were recorded, and Delta(13)C, delta(15)N, and the concentration of nitrogen (N), phosphorus, and several ions (K(+), Na(+), Ca(2+), Mg(2+)) were analysed in shoot material. Compared with control conditions (full irrigation with Hoagland normal) all other treatments inhibited photosynthesis through stomatal closure, accelerated senescence, and decreased biomass. Full irrigation with 12 dS m(-1) outperformed other stress treatments in terms of biomass production and physiological performance. Biomass correlated positively with N and delta(15)N, and negatively with Na(+) across genotypes and fully irrigated treatments, while relationships across deficit irrigation conditions were weaker or absent. Delta(13)C did not correlate with biomass across treatments, but it was the best trait correlating with phenotypic differences in biomass within treatments. Tritordeum produced more biomass than durum wheat in all treatments. Its low Delta(13)C and high K(+)/Na(+) ratio, together with a high potential growth, may underlie this finding. Mechanisms relating delta(15)N and Delta(13)C to biomass are discussed.

This investigation evaluated the effects of a 13-month deployment to Iraq on body composition and selected fitness measures. Seventy-three combat arms soldiers were measured pre- and postdeployment. Body composition was assessed by dual X-ray absorptiometry (DXA). Strength was measured by single repetition maximum (1-RM) lifts on bench press and squat. Power was assessed by a bench throw and squat jump. Aerobic endurance was evaluated with a timed 2-mile run. Exercise and injury history were assessed by questionnaire. Upper and lower body strength improved by 7% and 8%, respectively (p < 0.001). Upper body power increased 9% (p < 0.001) and lean mass increased 3% (p < 0.05). In contrast, aerobic performance declined 13% (p < 0.001) and fat mass increased 9% (p < 0.05). Fewer soldiers participated in aerobic exercise or sports during deployment (p < 0.001). Unit commanders should be aware of potential fitness and body composition changes during deployment and develop physical training programs to enhance fitness following deployment.

Activated protein C (APC) resistance is commonly tested in hypercoagulation evaluations, and argatroban is an anticoagulant therapy used in hypercoagulable patients. The effect of argatroban on APC resistance testing is unknown. We studied 100 ex vivo specimens from 44 patients treated with argatroban. Argatroban increased the APC resistance ratio in all but 1 patient. The effect was seen even in the specimens containing subtherapeutic argatroban levels. For patients without APC resistance, the mean APC resistance ratio significantly increased from 2.43 without argatroban to 3.10 with argatroban. For patients with APC resistance due to factor V Leiden, argatroban significantly increased the mean ratio from 1.73 to 2.13, falsely raising it into the normal range (>2). Argatroban increases the APC resistance ratio, which can mask a diagnosis of APC resistance and, therefore, factor V Leiden. Clinicians should be advised that APC resistance testing for patients receiving argatroban is not valid.

Several clinical studies have suggested that blood transfusions are immunosuppressive. Whereas there have been reports describing immunosuppression induced by leukocytes or fragments thereof, the possibility that microparticles, released by erythrocytes during storage, are also involved was not investigated. We present evidence here that such microparticles have all the properties of ectosomes including size, the presence of a lipid membrane, and the specific sorting of proteins. These erythrocyte-derived ectosomes (E-ecto) fixed C1q, which was followed by activation of the classical pathway of complement with binding of C3 fragments. Similarly to ectosomes released by PMN, they express phosphatidylserine on their surface membrane, suggesting that they may react with and down-regulate cells of the immune system. In vitro, they were taken up by macrophages, and they significantly inhibited the activation of these macrophages by zymosan A and LPS, as shown by a significant drop in TNF-alpha and IL-8 release (respectively, 80% and 76% inhibitions). In addition, the effect of E-ecto was not transient but lasted for at least 24 h. In sum, E-ecto may interfere with the innate immune system/inflammatory reaction. Therefore, E-ecto transfused with erythrocytes may account for some of the immunosuppressive properties attributed to blood transfusions.

We report that use of the popular analgesic tramadol can cause false-positive urine buprenorphine results. We examined the extent of tramadol cross-reactivity in three point-of-care urine buprenorphine immunoassays (ACON, QuikStrip, and ABMC) and an instrument-based one (Cedia). We tested 29 urine samples from patients known to be taking tramadol. Ten different samples tested positive for urine buprenorphine by at least one immunoassay. Samples with positive buprenorphine screens by immunoassay were tested for total buprenorphine and total norbuprenorphine content by liquid chromatography-tandem mass spectrometry (LC-MS-MS), which confirmed that seven of the 10 positive samples were false-positives. The remaining three positive immunoassay samples had insufficient quantity for LC-MS-MS testing. No false-positives were detected with the ACON (10 ng/mL calibration cutoff) or the Cedia assay (using a 20 ng/mL calibration cutoff). All four false-positive Cedia results (using a 5 ng/mL cutoff) in this study tested negative using the ACON device. Our data suggest that tramadol use can cause false-positive urine buprenorphine immunoassays, and this effect appears to be assay-dependent. Tramadol interference with the Cedia assay is clinically relevant, especially if the 5 ng/mL calibration cutoff is used.

This retrospective study was conducted to assess the nature and causes of serious oral-facial illnesses and injuries among U.S. Army personnel deployed to Iraq and Afghanistan in 2003 and 2004. Information for this study came from the U.S. Air Force Transportation Regulating and Command & Control Evacuation System database for medical evacuations (MEDEVACS) for 2003 to 2004. The study found 327 oral-facial MEDEVACS out of Iraq (cumulative incidence: 11/10,000 soldiers per year) and 47 out of Afghanistan (cumulative incidence: 21/10,000 soldiers per year), for a total of 374 MEDEVACS. Forty-two percent (n = 158) of all oral-facial MEDEVACS were due to diseases of the oral cavity, salivary glands, and jaw. Another 36% (n = 136) of oral-facial MEDEVACS were for battle injuries, primarily fractures of the mandible, caused by acts of war. Twenty-one percent (n = 80) of oral-facial MEDEVACS were due to nonbattle injuries, primarily fractures of the mandible, mainly caused by motor vehicle accidents and fighting.

Gene transfer has been used to correct inherited immunodeficiencies, but in several patients integration of therapeutic retroviral vectors activated proto-oncogenes and caused leukemia. Here, we describe improved methods for characterizing integration site populations from gene transfer studies using DNA bar coding and pyrosequencing. We characterized 160,232 integration site sequences in 28 tissue samples from eight mice, where Rag1 or Artemis deficiencies were corrected by introducing the missing gene with gamma-retroviral or lentiviral vectors. The integration sites were characterized for their genomic distributions, including proximity to proto-oncogenes. Several mice harbored abnormal lymphoproliferations following therapy--in these cases, comparison of the location and frequency of isolation of integration sites across multiple tissues helped clarify the contribution of specific proviruses to the adverse events. We also took advantage of the large number of pyrosequencing reads to show that recovery of integration sites can be highly biased by the use of restriction enzyme cleavage of genomic DNA, which is a limitation in all widely used methods, but describe improved approaches that take advantage of the power of pyrosequencing to overcome this problem. The methods described here should allow integration site populations from human gene therapy to be deeply characterized with spatial and temporal resolution.

This study describes injury rates, injury diagnoses, anatomical locations of injuries, limited duty days, and activities associated with injuries in a sample of Army mechanics. Medical records of 518 male and 43 female Army mechanics were screened for injuries during 1 year at a large U.S. Army installation. Weight, height, age, and ethnicity were also extracted from the medical records. Body mass index was calculated as weight/height2. Overall injury rates for men and women were 124 and 156 injuries/100 person-years, respectively, with a rate of 127 injuries/100 person-years for all soldiers combined. Women had higher overuse injury rates while men had higher traumatic injury rates. Limited duty days for men and women were 2,076 and 1,966 days/100 person-years, respectively. The lower back, knee, ankle, foot, and shoulder involved 61% of the injuries. Activities associated with injury included (in order of incidence) physical training, mechanical work, sports, airborne-related activities, road marching, garrison/home activities, and chronic conditions. Among the men, elevated injury risk was associated with higher body weight and higher body mass index. It may be possible to prevent many injuries by implementation of evidenced-based interventions currently available in the literature.

Epidemiological studies often have to rely on a participant's self-reporting of information. The validity of the self-report instrument is an important consideration in any study. The purpose of this investigation was to determine the validity of self-reported Army Physical Fitness Test (APFT) scores. The APFT is administered to all soldiers in the U.S. Army twice a year and consists of the maximum number of push-ups completed in 2 minutes, the maximum number of sit-ups completed in 2 minutes, and a 2-mile run for time. Army mechanics responded to a questionnaire in March and June 2004 asking them to report the exact scores of each event on their most recent APFT. Actual APFT scores were obtained from the soldier's military unit. The mean +/- standard deviation (SD) of actual and self-reported numbers of push-ups was 61 +/- 14 and 65 +/- 13, respectively. The mean +/- SD of actual and self-reported numbers of sit-ups were 66 +/- 10 and 68 +/- 10, respectively. The mean +/- SD of actual and self-reported run times (minutes) were 14.8 +/- 1.4 and 14.6 +/- 1.4, respectively. Correlations between actual and self-reported push-ups, sit-ups, and run were 0.83, 0.71, and 0.85, respectively. On average, soldiers tended to slightly over-report performance on all APFT events and individual self-reported scores could vary widely from actual scores based on Bland-Altman plots. Despite this, the close correlations between the actual and self-reported scores suggest that self-reported values are adequate for most epidemiological military studies involving larger sample sizes.

This study describes injury and illness rates and some risk factors among soldiers from an armor division during a rotation at the National Training Center (Fort Irwin, California). Soldiers from a brigade of the 1st Cavalry Division were involved in a 5-week training exercise at the National Training Center. Health care visits were systematically recorded by the unit medics. Of 4,101 men and 413 women who participated in the exercise, 504 soldiers (409 men and 95 women) sought medical care at the main support medical clinic or Weed Army Community Hospital. The rates of injury and illness visits were 1.2% and 0.6% per week for men and 2.3% and 2.2% per week for women, respectively. Women had twice the risk of an injury and 3.5 times the risk of an illness, compared with men. Compared with other branches, combat service support soldiers had higher rates of injuries and illnesses. Enlisted soldiers of lower rank (E1-E4) experienced higher injury and illness rates than did noncommissioned officers and commissioned officers. Musculoskeletal injuries, environmental conditions, and dermatological conditions accounted for most visits.

Background: Anti-C1q antibodies (anti-C1q) have been shown to correlate positively with systemic lupus erythematosus (SLE) nephritis. Several clinical studies indicated a high negative predictive value, suggesting that active lupus nephritis is rarely seen in patients with no anti-C1q. However, the true prevalence of anti-C1q at the time of active lupus nephritis has not been well established. The aim of this study was to determine prospectively the prevalence of anti-C1q in proven active lupus nephritis at the time of the renal biopsy., Methods: In this prospective multi-centre study, we investigated adult SLE patients undergoing renal biopsy for suspected active lupus nephritis. Serum samples were taken at the time of the biopsy and analysed for the presence of anti-C1q in a standardized way. The activity of lupus nephritis was classified according to the renal histology. Biopsies were also analysed for the presence of glomerular IgG, C1q and C3 deposition., Results: A total of 38 patients fulfilling at least 4/11 American College of Rheumatology (ACR) criteria for the diagnosis of SLE were included. Out of this, 36 patients had proliferative (class II, III or IV) and two had class V lupus nephritis. All but one patient with proliferative lupus nephritis were positive for anti-C1q (97.2%) compared with the 35% of control SLE patients with inactive lupus nephritis and 25% of SLE patients without lupus nephritis ever. All patients were positive for glomerular C1q (36/36) and 37/38 patients had glomerular IgG deposits. Anti-C1q strongly decreased during successful treatment., Conclusions: Anti-C1q have a very high prevalence in biopsy-proven active lupus nephritis, thus a negative test result almost excludes active nephritis. The data support the hypothesis of a pathogenic role of anti-C1q in lupus nephritis.

During the first few days of Army Basic Combat Training (BCT), recruits take a running test and after completing this test they are ranked from fast to slow. Four roughly equal-sized "ability groups" are established from these rankings and recruits run together in these groups for their physical training during BCT. In the past, there has been no formal guidance regarding how fast or how far these ability groups should run. To fill this void, this study provides guidance for running speeds and distances during BCT. The major considerations included are: (1) minimizing injuries, (2) the initial aerobic fitness level of recruits, (3) historical improvements in run times during BCT, (4) historical running speeds of the slower individuals in each ability group, (5) running speeds that must be achieved to "pass" the 2-mile run in BCT, (6) the gender composition of the ability groups, and (7) recommendations from the trainers and field testing. Three databases were analyzed that contained a total of 16,716 men and 11,600 women. Four steps were used in the analyses: (1) establishment of run-time cut points for representative ability groups, (2) determination of initial (starting) run speeds, (3) estimation of changes in run speeds with training, and (4) establishment of run speeds and distances for each week of BCT. Efforts were made to (1) keep the running speeds between 70% and 83% of the estimated maximal oxygen uptake (VO2max) for all ability groups, (2) consider the 2-mile running pace of the slower individuals in each ability group, and (3) keep the total running distance for the two slower ability groups below a total of 25 miles, the apparent threshold for increasing injury incidence. A chart provides speeds and distances for each ability group at each week of BCT. Using these recommended speeds and distances should allow trainees to improve their aerobic fitness, pass the Army Physical Fitness Test, and minimize injuries that result in lost training time and, ultimately, lower fitness levels.

Recruits arriving for basic combat training (BCT) between October 1999 and May 2004 were administered an entry-level physical fitness test at the reception station. If they failed the test, then they entered the Fitness Assessment Program (FAP), where they physically trained until they passed the test and subsequently entered BCT. The effectiveness of the FAP was evaluated by examining fitness, injury, and training outcomes. Recruits who failed the test, trained in the FAP, and entered BCT after passing the test were designated the preconditioning (PC) group (64 men and 94 women). Recruits who failed the test but were allowed to enter BCT without going into the FAP were called the no preconditioning (NPC) group (32 men and 73 women). Recruits who passed the test and directly entered BCT were designated the no need of preconditioning (NNPC) group (1,078 men and 731 women). Army Physical Fitness Test (APFT) scores and training outcomes were obtained from a company-level database, and injured recruits were identified from cases documented in medical records. The proportions of NPC, PC, and NNPC recruits who completed the 9-week BCT cycle were 59%, 83%, and 87% for men (p < 0.01) and 52%, 69%, and 78% for women (p < 0.01), respectively. Because of attrition, only 63% of the NPC group took the week 7 APFT, compared with 84% and 86% of the PC and NNPC groups, respectively. The proportions of NPC, PC, and NNPC recruits who passed the final APFT after all retakes were 88%, 92%, and 98% for men (p < 0.01) and 89%, 92%, and 97% for women (p < 0.01), respectively. Compared with NNPC men, injury risk was 1.5 (95% confidence interval, 1.0-2.2) and 1.7 (95% confidence interval, 1.0-3.1) times higher for PC and NPC men, respectively. Compared with NNPC women, injury risk was 1.2 (95% confidence interval, 0.9-1.6) and 1.5 (95% confidence interval, 1.1-2.1) times higher for PC and NPC women, respectively. This program evaluation showed that low-fit recruits who preconditioned before BCT had reduced attrition and tended to have lower injury risk, compared with recruits of similar low fitness who did not precondition.

The objective of this prospective, observational clinical study was to evaluate the safety and efficacy of once-daily and twice-daily directly observed therapy (DOT) in human immunodeficiency virus (HIV)-infected patients undergoing methadone treatment. Methadone and highly active antiretroviral therapy (HAART) were dispensed daily as DOT, with patients in the twice-daily HAART group self-administering the second dose. Clinical and laboratory end points were monitored, along with the impact of ongoing cocaine use. We studied 54 patients coinfected with HIV and hepatitis C virus. At baseline, the median virus load was 111,000 copies/mL, and the median CD4+ cell count was 165 cells/mm3. After a median of 24 months, 17 of 29 patients in the once-daily HAART group and 18 of 25 in the twice-daily HAART group had virus loads of <400 copies/mL, regardless of ongoing cocaine use. Thirty-two patients required methadone dose adjustment, which was managed without modification of HAART. Treatment-limiting hepatic toxicity was rare. A DOT program of coadministered methadone and HAART can be implemented with good results, even for patients who continue to use cocaine.