A survey of retail prices of antimicrobial products used in small-scale chicken farms in the Mekong Delta of Vietnam.
In the Mekong Delta region of Vietnam, high quantities of products containing antimicrobial are used as prophylactic and curative treatments in small-scale chicken flocks. A large number of these contain antimicrobial active ingredients (AAIs) considered of 'critical importance' for human medicine according to the World Health Organization (WHO). However, little is known about the retail prices of these products and variables associated with the expense on antimicrobials at farm level. Therefore, the aims of the study were: (1) to investigate the retail price of antimicrobials with regards to WHO importance criteria; and (2) to quantify the antimicrobial expense incurred in raising chicken flocks. We investigated 102 randomly-selected small-scale farms raising meat chickens (100-2000 per flock cycle) in two districts in Dong Thap (Mekong Delta) over 203 flock production cycles raised in these farms. Farmers were asked to record the retail prices and amounts of antimicrobial used. A total of 214 different antimicrobial-containing products were identified. These contained 37 different AAIs belonging to 13 classes. Over half (60.3%) products contained 1 highest priority, critically important AAI, and 38.8% 1 high priority, critically important AAI. The average (farm-adjusted) retail price of a daily dose administered to a 1 kg bird across products was 0.40 cents of 1 US$ (₵) (SE ± 0.05). The most expensive products were those that included at least one high priority, critically important AAI, as well as those purchased in one of the two study districts. Farmers spent on average of ₵3.91 (SE ± 0.01) on antimicrobials per bird over the production cycle. The expense on antimicrobials in weeks with disease and low mortality was greater than on weeks with disease and high mortality, suggesting that antimicrobial use had a beneficial impact on disease outcomes (χ2 = 3.8; p = 0.052). Farmers generally used more expensive antimicrobials on older flocks. The retail prices of antimicrobial products used in chicken production in Mekong Delta small-scale chicken farms are very low, and not related to their relevance for human medicine. Farmers, however, demonstrated a degree of sensitivity to prices of antimicrobial products. Therefore, revising pricing policies of antimicrobial products remains a potential option to curb the use of antimicrobials of critical importance in animal production.


Assessment of topical corticosteroid ointment on postcesarean scars prevention: A prospective clinical trial.
To evaluate the effectiveness of corticosteroid ointment in hypertrophic scars prevention following Cesarean section. This study was conducted between June 2017-May 2018 in Acıbadem Kozyatagı Hospital. Sixty-one patients (31 treatment and 30 control patients) took part in the current study which evaluated wound outcomes and patient satisfaction. All patients' wound characteristics were assessed via the modified Vancouver Scar Scale (MVSS) score (height, pigmentation, vascularity, and pliability) at baseline (post-op 10th day), three months and six months. The treatment group received corticosteroid cream every other day for three months. Comparative evaluations and time-bound changes were evaluated in both groups. The mean age of the subjects was 31.28 ± 3.95 years. While the height and vascularity subsection scores of corticosteroid recipients were significantly reduced compared to those without treatment at three months, the scores were similar at six months. Furthermore, pliability and pigmentation decreased equally in both groups. There was high satisfaction with scar healing in the experimental group (20%, n=6), while 12.9% (n=4) of the patients were satisfied in the control group. Two patients reported itching after treatment. The clinical outcomes in both groups were similar. Although vascularity and height parameters improved in three months, similar results were also observed in the group that did not receive treatment after the end of six months. This may have been due to the fact that treatment was stopped after three months. We recommend that the hypothesis be tested in larger series in future studies.


Laser speckle contrast imaging of cerebral blood flow.
Laser speckle contrast imaging (LSCI) has emerged over the past decade as a powerful, yet simple, method for imaging of blood flow dynamics in real time. The rapid adoption of LSCI for physiological studies is due to the relative ease and low cost of building an instrument as well as the ability to quantify blood flow changes with excellent spatial and temporal resolution. Although measurements are limited to superficial tissues with no depth resolution, LSCI has been instrumental in pre-clinical studies of neurological disorders as well as clinical applications including dermatological, neurosurgical and endoscopic studies. Recently a number of technical advances have been developed to improve the quantitative accuracy and temporal resolution of speckle imaging. This article reviews some of these recent advances and describes several applications of speckle imaging.


Exposure to environmentally-relevant concentrations of hexavalent chromium does not induce ovarian toxicity in mice.
Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water (≥250 ppm) is reported to decrease ovarian follicle counts and increase follicular atresia in mice. To assess effects at lower concentrations, herein we exposed B6C3F1 mice to 0.1-150 ppm Cr(VI) in drinking water for 90 days in a GLP-compliant study. Ovarian follicular counts, differentiation, and degeneration were assessed from every 10th serial section (up to 14 sections per ovary). Ovarian follicular counts, differentiation, and rate of atresia were not altered in any exposure group. Gross and microscopic changes were not apparent in any of the evaluated reproductive or glandular organs. The no observable adverse effect level (NOAEL) for follicular effects was 150 ppm. In addition to these findings, published Cr(VI) studies examining follicles were scored using two methods for assessing study quality for use in risk assessment-including the Toxic Substance Control Act (TSCA) scoring method. Both methods revealed that studies reporting adverse effects on follicles generally received low scores. Overall, the current study indicates no/low potential for Cr(VI) to induce follicular toxicity in mice below 150 ppm Cr(VI) in drinking water (17.7 mg/kg bodyweight).


Cross-talk signals in the CNS: role of neurotrophic and hormonal factors, adhesion molecules and intercellular signaling agents in luteinizing hormone-releasing hormone (LHRH)-astroglial interactive network.
Neuron-astrocyte interactions play a crucial role during development and in the adult brain. During development, glial cells are involved in the guidance of neuronal precursors and in extending neuronal fiber projections. Astrocytes can promote neurite outgrowth, both "in vitro" and "in vivo". In the central nervous system (CNS), they express receptors for a variety of growth factors (GFs), neurotransmitters and/or neuromodulators. In turn, neuronal cells can respond to astrocyte-derived growth factors and control astrocyte function via a common set of signaling molecules and intracellular transducing pathways. It is also well established that astrocytes are involved with regenerative failure within the CNS following injury. Increasing evidence support the viewpoint that soluble factors from lymphoid/mononuclear cells modulate the growth and function of cells found in the CNS, specifically macroglia and microglia cells. Furthermore, glial cells can secrete immunoregulatory molecules that influence immune cells, as well as the glial cells themselves. In recent years, a bi-directional flow of informational molecules between LHRH neurons, subserving the neuroendocrine control of reproductive function, and astroglia cells has been disclosed. During their maturation and differentiation in vitro, astroglial cells release peptide growth factors that markedly accelerate LHRH neuronal phenotypic differentiation . In addition, these peptides induce the acquisition of mature LHRH secretory potential, with a potency depending on both the "age" and the specific brain localization of the astroglia, as well as the degree of LHRH neuronal differentiation "in vitro". Different experimental paradigms such as co-culture and mixed culture models between the GT1-1 neurons and astroglial cells in primary culture, disclosed the presence of a bi-directional flow of informational molecules regulating both proliferative and secretory capacities of each cell type. Growth factors are key players in LHRH neuron-astroglia crosstalk. In particular, basic fibroblast growth factor (bFGF) was identified as a major differentiation factor for the immortalized hypothalamic LHRH neuronal cell line. A specific synergy/cooperation between bFGF and other growth factors was also revealed at specific stages of LHRH neuron differentiation, indicating that the sequential expression of specific growth factors may participate in the processes of LHRH neuron migration, differentiation and functional regulation. Since bFGF is expressed in GT1-1 neurons and glial cells a possible paracrine/autocrine regulatory loop is suggested. Indeed, neutralization experiments aimed at counteracting endogenous bFGF during neuron-glia interactions dramatically inhibited astroglia neurotrophic effects. On the other hand, the importance of adhesion molecules in cell-to-cell communication was underscored by the significant inhibition of GT1-1 LHRH production and cell proliferation following the counteraction of neuron-neuron/neuron-glia interactions through addition of neuronal cell adhesion molecule (N-CAM) antiserum. Other information came from pharmacological experiments manipulating the astroglial-derived cytokines and/or nitric oxide, which revealed a crosstalk between the neuronal and astroglial compartments. From the bulk of this information, it seems likely that interactions between astroglia and LHRH neurons play a major role in the integration of the multiplicity of brain signals converging on the LHRH neurons that govern reproduction.


An in vitro comparison of standard cleaning to a continuous passive disinfection cap for the decontamination of needle-free connectors.
The optimal decontamination method for needle-free connectors is still unresolved. The objective of this study was to determine if a continuous passive disinfection cap is as effective as standard cleaning for the microbial decontamination of injection ports of two types of needle-free connectors. The injection ports of needle-free connectors were inoculated with Staphylococcus aureus and allowed to dry. Disinfection caps containing 70% (v/v) isopropyl alcohol (IPA) were attached to the connectors for one, three or 7 days and were compared with needle-free connectors cleaned with 2% (w/v) chlorhexidine gluconate (CHG) in 70% (v/v) IPA. The number of S. aureus remaining on the injection ports was evaluated. Median log10 reductions and 95% confidence interval (CI) were calculated and data analyzed using the Mann-Whitney test. The application of the disinfection cap resulted in a significantly higher reduction in S. aureus than the 2% (w/v) CHG in 70% (v/v) IPA wipe, achieving a > 5 Log10 reduction in CFU at each time point. The disinfection caps resulted in a significantly higher reduction in S.aureus on the injection ports when compared to the use of a 2% (w/v) CHG in 70% (v/v) IPA wipe. This offers an explanation for the lower rates of central-line associated bloodstream infection (CLABSI) associated with the use of disinfection caps reported in clinical studies.


Implication of folate deficiency in CYP2U1 loss of function.
Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders. Understanding of their pathogenic mechanisms remains sparse, and therapeutic options are lacking. We characterized a mouse model lacking the Cyp2u1 gene, loss of which is known to be involved in a complex form of these diseases in humans. We showed that this model partially recapitulated the clinical and biochemical phenotypes of patients. Using electron microscopy, lipidomic, and proteomic studies, we identified vitamin B2 as a substrate of the CYP2U1 enzyme, as well as coenzyme Q, neopterin, and IFN-α levels as putative biomarkers in mice and fluids obtained from the largest series of CYP2U1-mutated patients reported so far. We also confirmed brain calcifications as a potential biomarker in patients. Our results suggest that CYP2U1 deficiency disrupts mitochondrial function and impacts proper neurodevelopment, which could be prevented by folate supplementation in our mouse model, followed by a neurodegenerative process altering multiple neuronal and extraneuronal tissues.


Simultaneous assessment of autophagy and apoptosis using multispectral imaging cytometry.
Multiple stress pathways result in the induction of autophagy and apoptosis. Current methods (e.g., protein gel blot, microscopy) do not offer quantitative single-cell resolution, thus making it difficult to discern if these pathways are mutually exclusive or, in some situations, cooperative in executing cell death. We report a novel method that enables high-throughput, high-content assessment of LC3 puncta and caspase-3 cleavage at the single cell level.


Differences in severity at admission for heart failure between rural and urban patients: the value of adding laboratory results to administrative data.
Rural/urban variations in admissions for heart failure may be influenced by severity at hospital presentation and local practice patterns. Laboratory data reflect clinical severity and guide hospital admission decisions and treatment for heart failure, a costly chronic illness and a leading cause of hospitalization among the elderly. Our main objective was to examine the role of laboratory test results in measuring disease severity at the time of admission for inpatients who reside in rural and urban areas. We retrospectively analyzed discharge data on 13,998 hospital discharges for heart failure from three states, Hawai'i, Minnesota, and Virginia. Hospital discharge records from 2008 to 2012 were derived from the State Inpatient Databases of the Healthcare Cost and Utilization Project, and were merged with results of laboratory tests performed on the admission day or up to two days before admission. Regression models evaluated the relationship between clinical severity at admission and patient urban/rural residence. Models were estimated with and without use of laboratory data. Patients residing in rural areas were more likely to have missing laboratory data on admission and less likely to have abnormal or severely abnormal tests. Rural patients were also less likely to be admitted with high levels of severity as measured by the All Patient Refined Diagnosis Related Groups (APR-DRG) severity subclass, derivable from discharge data. Adding laboratory data to discharge data improved model fit. Also, in models without laboratory data, the association between urban compared to rural residence and APR-DRG severity subclass was significant for major and extreme levels of severity (OR 1.22, 95% CI 1.03-1.43 and 1.55, 95% CI 1.26-1.92, respectively). After adding laboratory data, this association became non-significant for major severity and was attenuated for extreme severity (OR 1.12, 95% CI 0.94-1.32 and 1.43, 95% CI 1.15-1.78, respectively). Heart failure patients from rural areas are hospitalized at lower severity levels than their urban counterparts. Laboratory test data provide insight on clinical severity and practice patterns beyond what is available in administrative discharge data.


PAK1 is a novel MEK-independent raf target controlling expression of the IAP survivin in M-CSF-mediated osteoclast survival.
As activation of the Ras/Raf/MEK/ERK pathway is a critical component of M-CSF-promoted osteoclast survival, determining specific mechanism by which M-CSF activates this signal transduction pathway is paramount towards advancing treatment of pathological conditions resulting in increased bone turnover. The p21 activated kinase PAK1 modulates activation of the Raf/MEK/ERK pathway by either directly activating Raf or priming MEK for activation by Raf. Therefore a role for PAK1 in M-CSF-mediated activation of the MEK/ERK pathway controlling osteoclast survival was assessed. Here we show that PAK1 is activated by M-CSF in a Ras-dependent mechanism that promotes osteoclast survival. Surprisingly, PAK1 did not modulate Raf activation or Raf-mediated MEK activation. M-CSF mediated activation of Raf was required for PAK1 activation and osteoclast survival promoted by PAK1. This survival response was MEK-independent as expression of constitutively active MEK did not rescue osteoclasts from apoptosis induced by blocking PAK1 function. Functionally, PAK1 promoted osteoclast survival by modulating expression of the IAP family member Survivin. M-CSF therefore functions to promote PAK1 activation as a novel MEK-independent Raf target to control Survivin-mediated osteoclast survival.


Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis.
To determine genome-wide methylation profiles of bone from patients with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures. Trabecular bone pieces were obtained from the central part of the femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA was isolated, and methylation was explored with Illumina methylation arrays. RNA was extracted, pooled, and deep-sequenced to obtain the whole transcriptome. Differentially methylated regions were identified, and connections between genes with differentially methylated regions were explored by pathway and text-mining analyses. After quality control, methylation of 23,367 CpG sites (13,463 genes) was analyzed. There was a genome-wide inverse relationship between methylation and gene expression in both patient groups. Comparison of OP and OA bones revealed 241 CpG sites, located in 228 genes, with significant differences in methylation (false discovery rate<0.05). Of them, 217 were less methylated in OP than in OA. The absolute methylation differences were >5% in 128 CpG sites and >10% in 45 CpG sites. The differentially methylated genes were enriched for association with bone traits in the genome-wide association study catalog. Pathway analysis and text-mining analysis with Gene Relationships Across Implicated Loci software revealed enrichment in genes participating in glycoprotein metabolism or cell differentiation, and particularly in the homeobox superfamily of transcription factors. Genome-wide methylation profiling of bone samples revealed differentially methylated regions in OP and OA. These regions were enriched in genes associated with cell differentiation and skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the existence of a developmental component in the predisposition to these disorders.


Health of adults caring for orphaned children in an HIV-endemic community in South Africa.
In South Africa, an estimated 2.5 million children have been orphaned by AIDS and other causes of adult mortality. Although there is a growing body of research on the well-being of South African orphaned children, few research studies have examined the health of adult individuals caring for children in HIV-endemic communities. The cross-sectional survey assessed prevalence of general health and functioning (based on Short-Form 36 version 2 scale), depression (based on Center for Epidemiologic Studies-Depression scale), anxiety (using Kessler-10 scale), and post-traumatic stress (using the Harvard Trauma Questionnaire) among a representative community sample of adults caring for children in Umlazi Township, an HIV-endemic community in South Africa. Of 1599 respondents, 33% (n=530) were carers of orphaned children. Results showed that, overall, carers reported poor general health and functioning and elevated levels of depression, anxiety, and post-traumatic stress. Carers of orphaned children reported significantly poorer general health and functioning and higher rates of depression and post-traumatic stress compared with carers of non-orphaned children. In multivariate analyses, orphan carer and non-orphan carer differences in general health were accounted for by age, gender, education, economic assets, and source of income, but differences in depression were independent of these cofactors. Interventions are needed to address physical and mental health of carers in general. Greater health problems among orphan carers appeared to be fully explained by socioeconomic characteristics, which offer opportunities for targeting of programs. More research is needed to understand determinants of mental health disparities among orphan carers, which were not explained by socioeconomic characteristics.


Optimal soil carbon sampling designs to achieve cost-effectiveness: a case study in blue carbon ecosystems.
Researchers are increasingly studying carbon (C) storage by natural ecosystems for climate mitigation, including coastal 'blue carbon' ecosystems. Unfortunately, little guidance on how to achieve robust, cost-effective estimates of blue C stocks to inform inventories exists. We use existing data (492 cores) to develop recommendations on the sampling effort required to achieve robust estimates of blue C. Using a broad-scale, spatially explicit dataset from Victoria, Australia, we applied multiple spatial methods to provide guidelines for reducing variability in estimates of soil C stocks over large areas. With a separate dataset collected across Australia, we evaluated how many samples are needed to capture variability within soil cores and the best methods for extrapolating C to 1 m soil depth. We found that 40 core samples are optimal for capturing C variance across 1000's of kilometres but higher density sampling is required across finer scales (100-200 km). Accounting for environmental variation can further decrease required sampling. The within core analyses showed that nine samples within a core capture the majority of the variability and log-linear equations can accurately extrapolate C. These recommendations can help develop standardized methods for sampling programmes to quantify soil C stocks at national scales.


Ultrasonic imaging of seismic physical models using a phase-shifted fiber Bragg grating.
We report what is to our knowledge the first ultrasonic imaging of seismic physical models by using a phase-shifted fiber Bragg grating (PS-FBG). Seismic models, which consist of multiple layer structures, were immersed in water. Piezoelectric (PZT) transducer was used to generate ultrasonic waves and a PS-FBG as a receiver. Two-dimensional (2D) ultrasonic images were reconstructed by scanning the PS-FBG with a high-precision position scanning device. In order to suppress the low-frequency drift of the Bragg wavelength during scanning, a tight wavelength tracking method was employed to lock the laser to the PS-FBG resonance in its reflection bandgap. The ultrasonic images captured by the PS-FBG have been compared with the images obtained by the geophysical imaging system, Sinopec, demonstrating the feasibility of our PS-FBG based imaging system in seismic modeling studies.


Are there "stages of change" in the practice of female genital cutting?: Qualitative research findings from Senegal and The Gambia.
In recent years there has been growing interest in developing theoretical models for understanding behaviour change with respect to the practice of female genital cutting (FGC). Drawing on extensive qualitative data collected in Senegal and The Gambia, the research reported here explores whether and how theoretical models of stages of behaviour change can be applied to FGC. Our findings suggest that individual readiness to change the practice of FGC is most dearly seen as operating along a continuum, and that broad stages of change characterise regions or segments of this continuum. Stages identified by previous researchers for other "problems behaviours" such as smoking inadequately describe readiness to change FGC since this decision is often a collective rather than individual one. The data reveal that the concept of stage of change is a complex construct that simultaneously captures behaviour, motivation, and features of the environment in which the decision is being made. Consequently stages identified in this research reflect the multidimensional nature of readiness to change the practice of FGC. Limitations of stage of change models as applied to FGC include the fact that they do not capture important aspects of the dynamics of negotiation between decision-makers, and do not reflect the shifting nature of opinions of individuals or the constellation of decision-makers. Nonetheless, we suggest the application of stage of change theory may provide a useful means of describing readiness for change of individual decisions-makers and at an aggregate level, patterns of readiness for change in a community. How this construct can be employed in quantitative population research requires further investigation.


Insights into respiratory disease through bioinformatics.
Respiratory diseases such as asthma, chronic obstructive pulmonary disease and lung cancer represent a critical area for medical research as millions of people are affected globally. The development of new strategies for treatment and/or prevention, and the identification of biomarkers for patient stratification and early detection of disease inception are essential to reducing the impact of lung diseases. The successful translation of research into clinical practice requires a detailed understanding of the underlying biology. In this regard, the advent of next-generation sequencing and mass spectrometry has led to the generation of an unprecedented amount of data spanning multiple layers of biological regulation (genome, epigenome, transcriptome, proteome, metabolome and microbiome). Dealing with this wealth of data requires sophisticated bioinformatics and statistical tools. Here, we review the basic concepts in bioinformatics and genomic data analysis and illustrate the application of these tools to further our understanding of lung diseases. We also highlight the potential for data integration of multi-omic profiles and computational drug repurposing to define disease subphenotypes and match them to targeted therapies, paving the way for personalized medicine.


Mechanisms from Food Insecurity to Worse HIV Treatment Outcomes in US Women Living with HIV.
Food insecurity (FI) contributes to HIV-related morbidity and mortality, but the mechanisms whereby FI negatively impacts HIV health are untested. We tested the hypothesis that FI leads to poor HIV clinical outcomes through nutritional, mental health, and behavioral paths. We analyzed data from Women's Interagency HIV Study (WIHS) among 1803 women living with HIV (WLWH) (8225 person-visits) collected from 2013 to 2015 biannually from nine sites across the United States participating in the WIHS. FI was measured with the US Household Food Security Survey Module. Outcomes included HIV viral nonsuppression, CD4 cell counts, and physical health status (PHS). We used longitudinal logistic and linear regression models with random effects to examine associations adjusting for covariates and path analysis to test nutritional, mental health, and behavioral paths. Increasing severity of FI was associated with unsuppressed viral load, lower CD4 counts, and worse PHS (all p < 0.05). Report of FI 6 months earlier was independently associated with most outcomes after adjusting for concurrent FI. For viral nonsuppression, the nutritional and behavioral paths accounted for 2.09% and 30.66% of the total effect, with the mental health path operating via serial mediation through the behavioral path. For CD4 count, the mental health and behavioral paths accounted for 15.21% and 17.0% of the total effect, respectively. For PHS, depressive symptoms accounted for 60.2% of the total effect. In conclusion, FI is associated with poor health among WLWH through different paths depending on the outcome. Interventions should target FI and its behavioral and mental health mechanisms to improve HIV outcomes.


Evaluation of an autotutorial-simulator program for instruction of hollow organ closure.
Forty students were randomly assigned into two study groups (traditional, T; and simulator, S) of 20 students each for a core operative practice laboratory. Students were randomly paired and their group assignment and identity remained anonymous to the evaluators throughout the study. Questionnaires were distributed to students to evaluate prior surgical experience and obtain learning resource use information. Before the evaluation sessions, both groups were given identical learning resource opportunities except students in Group S received hollow organ simulators and practice materials for gastrotomy closure. All students were forewarned that surgical instruction would not be available during the evaluation sessions. In the first live animal evaluation session, all student pairs were videotaped after which stomachs were harvested for gross evaluation of the surgical site. Group T performed an additional gastrotomy for video and gross evaluation 2 weeks later. Questionnaire, and gross and video evaluation results were compared statistically between groups and sessions. The hollow organ model did not suitably simulate live stomach tissue; the material was more fragile and stiff and suture cut-out was a problem even with appropriate suture tension and technique. The model was effective for teaching needle placement, instrument usage, creating proper tissue inversion, and methods to minimize instrument handling of tissue during gastrotomy closure. Prior practice with models did not boost student confidence during their live gastrotomy session. The autotutorials (ATs) were well received by students but did not sufficiently address how to manage mucosal eversion, suture tension, and bleeding encountered during live gastrotomy. AT viewing time positively correlated with mean total video score for Group T during both sessions. None of the students had prior experience performing hollow organ closure and no significant difference in experience level was evident between groups. Mean closure time was not significantly different between groups for session one (Group T, mean, 31.5 minutes, range, 18.4 to 53.4; Group S, mean, 28.2 minutes, range, 16.8 to 36), but was significantly reduced for session two (Group T, mean, 21.3 minutes, range, 13.9 to 31). This AT/simulator program does not significantly influence students' overall gastrotomy closure technique; gross and video evaluation scores were not significantly different between groups. Without instructor supervision, an additional gastrotomy experience did not improve surgical technique appreciably for Group T; however, these students performed the second procedure with more confidence and speed.(ABSTRACT TRUNCATED AT 400 WORDS)


Pulmonary infection with mycobacterium xenopi: review of treatment and response.
Forty seven patients (82% male) with pulmonary infection caused by Mycobacterium xenopi have been reviewed. Pre-existing lung disease was present in 35 (75%). In 21 patients the disease was characterised by a subacute illness developing over a period of two to four months, while in another 20 patients there was a longer history of chronic respiratory problems often associated with slowly progressive changes evident from chest radiographs. Response to treatment was poor and unpredictable, and was not related to the results of in vitro sensitivity tests, pre-existing lung disease, or mode of onset of symptoms. Eleven patients (23%) were cured with chemotherapy. The best drug regimen appeared to be rifampicin and isoniazid combined with either streptomycin or ethambutol. Another 12 (26%) showed favourable responses to drug treatment initially, but eventually relapsed. Four patients had progressive disease while receiving prolonged courses of chemotherapy. Resection was performed in five patients with resultant cure in four. Since the prognosis with drug treatment alone is so unpredictable it is suggested that resection might be part of first line treatment, and that it should usually be performed if patients fail to respond to initial chemotherapy or if they relapse.


Dengue, Urbanization and Globalization: The Unholy Trinity of the 21(st) Century.
Dengue is the most important arboviral disease of humans with over half of the world's population living in areas of risk. The frequency and magnitude of epidemic dengue have increased dramatically in the past 40 years as the viruses and the mosquito vectors have both expanded geographically in the tropical regions of the world. There are many factors that have contributed to this emergence of epidemic dengue, but only three have been the principal drivers: 1) urbanization, 2) globalization and 3) lack of effective mosquito control. The dengue viruses have fully adapted to a human-Aedes aegypti-human transmission cycle, in the large urban centers of the tropics, where crowded human populations live in intimate association with equally large mosquito populations. This setting provides the ideal home for maintenance of the viruses and the periodic generation of epidemic strains. These cities all have modern airports through which 10s of millions of passengers pass each year, providing the ideal mechanism for transportation of viruses to new cities, regions and continents where there is little or no effective mosquito control. The result is epidemic dengue. This paper discusses this unholy trinity of drivers, along with disease burden, prevention and control and prospects for the future.


Childhood vaccines in Uganda and Zambia: Determinants and barriers to vaccine coverage.
Improving childhood vaccine coverage is a priority for global health, but challenging in low and middle-income countries. Although previous research has sought to measure determinants of vaccination, most has limitations. We measure determinants using a clearly-defined hypothetical model, multi-faceted data, and modeling strategy that makes full use of the hypothesis and data. We use linked, cross-sectional survey data from households, health facilities, patients and health offices in Uganda and Zambia, and Bayesian Structural Equation Modeling to quantify the proportion of variance in childhood vaccination that is explained by key determinants, controlling for known confounding. We find evidence that the leading determinant of vaccination is different for different outcomes. For three doses of pentavalent vaccine, intent to vaccinate (on the part of the mother) is the leading driver, but for one dose of the vaccine, community access is a larger factor. For pneumococcal conjugate vaccine, health facility readiness is the leading driver. Considering specifically-modifiable determinants, improvements in cost, facility catchment populations and staffing would be expected to lead to the largest increase in coverage according to the model. This analysis measures vaccination determinants using improved methods over most existing research. It provides evidence that determinants should be approached in the context of relevant outcomes, and evidence of specific determinants that could have the greatest impact in these two countries, if targeted. Future studies should seek to improve our analytic framework, apply it in different settings, and utilize stronger study designs. Programs that focus on a particular determinant should use these results to select an outcome that is appropriate to measure their effectiveness. Vaccination programs in these countries should use our findings to better target interventions and continue progress against vaccine preventable diseases.


Quantitative Molecular Detection of Xanthomonas hortorum pv. carotae in Carrot Seed Before and After Hot-Water Treatment.
Molecular assays to detect and quantify DNA from viable cells of the seedborne pathogen Xanthomonas hortorum pv. carotae in carrot seed were developed and evaluated for use on nontreated and hot-water-treated seed lots. Both a TaqMan real-time polymerase chain reaction (PCR) assay and a loop-mediated isothermal amplification (LAMP) dilution endpoint assay detected and quantified DNA from viable pathogen cells after treatment of carrot seed washes with the live-dead discriminating dye propidium monoazide (PMA). The detection limits of the assays were approximately 101 CFU for pure cultures of X. hortorum pv. carotae, and 102 to 103 CFU/g seed from naturally infested carrot seed lots. X. hortorum pv. carotae in and on carrot seed was killed by soaking the seed in hot water (52°C for 25 min), and a subsequent PMA treatment of these hot-water-treated seed washes suppressed detection of the pathogen with both the real-time PCR and LAMP assays. For 36 commercial seed lots treated with PMA but not hot water, regression of colony counts of X. hortorum pv. carotae measured by dilution plating on a semiselective agar medium versus estimates of pathogen CFU determined by the molecular assays resulted in significant (P ≤ 0.05) linear relationships (R2 = 0.68 for the real-time PCR assay and 0.79 for the LAMP assay). The molecular assays provided quantitative estimates of X. hortorum pv. carotae infestations in carrot seed lots in <24 h, which is a significant improvement over the 7 to 14 days required to obtain results from the traditional dilution-plating assay.


Preimplantation genetic diagnosis and the 'new' eugenics.
Preimplantation genetic diagnosis (PID) is often seen as an improvement upon prenatal testing. I argue that PID may exacerbate the eugenic features of prenatal testing and make possible an expanded form of free-market eugenics. The current practice of prenatal testing is eugenic in that its aim is to reduce the numbers of people with genetic disorders. Due to social pressures and eugenic attitudes held by clinical geneticists in most countries, it results in eugenic outcomes even though no state coercion is involved. I argue that technological advances may soon make PID widely accessible. Because abortion is not involved, and multiple embryos are available, PID is radically more effective as a tool of genetic selection. It will also make possible selection on the basis of non-pathological characteristics, leading, potentially, to a full-blown free-market eugenics. For these reasons, I argue that PID should be strictly regulated.


Capability, opportunity, and motivation to enact hygienic practices in the early stages of the COVID-19 outbreak in the United Kingdom.
The COVID-19 pandemic is one of the greatest global health threats facing humanity in recent memory. This study aimed to explore influences on hygienic practices, a set of key transmission behaviours, in relation to the Capability, Opportunity, Motivation-Behaviour (COM-B) model of behaviour change (Michie et al., 2011). Data from the first wave of a longitudinal survey study were used, launched in the early stages of the UK COVID-19 pandemic. Participants were 2025 adults aged 18 and older, representative of the UK population, recruited by a survey company from a panel of research participants. Participants self-reported motivation, capability, and opportunity to enact hygienic practices during the COVID-19 outbreak. Using regression models, we found that all three COM-B components significantly predicted good hygienic practices, with motivation having the greatest influence on behaviour. Breaking this down further, the subscales psychological capability, social opportunity, and reflective motivation positively influenced behaviour. Reflective motivation was largely driving behaviour, with those highest in reflective motivation scoring 51% more on the measure of hygienic practices compared with those with the lowest scores. Our findings have clear implications for the design of behaviour change interventions to promote hygienic practices. Interventions should focus on increasing and maintaining motivation to act and include elements that promote and maintain social support and knowledge of COVID-19 transmission. Groups in particular need of targeting for interventions to increase hygienic practices are males and those living in cities and suburbs.


Gender-Based Violence among Married Women in Debre Tabor Town, Northwest Ethiopia: A Qualitative Study.
Gender-based violence is one of the major public health problems in Ethiopia. This study aimed to assess the perception and attitude of the community towards gender-based violence among married women in Northwest Ethiopia. A qualitative study was conducted using the purposive sampling technique for the three focus group discussions and ten in-depth interviews among married women. Data was analyzed thematically using version 3.4 of the Open Code Software. Most of the participants perceived that gender-based violence was acceptable in the community, violent acts needed to be considerably tolerated rather than condemned. Additionally, participants perceived that the consequences of gender-based violence were mild, and its elimination was difficult. Domestic violence was found to be common, marital rape was not clearly understood, and there was no tendency to disapprove it. This study revealed that the attitude of people and traditional norms played the major role in determining the acceptability of gender-based violence on married women. Increasing awareness on the consequences of gender-based violence, strengthening of women empowerment, involving different stakeholders on the provision of education, amending and enforcing the existing laws, and providing professional help to stop or reduce violence against women are recommended.


Effective vancomycin concentrations in children: a cross-sectional study.
Analyze the microbiological effectiveness, based on the pharmacokinetics/pharmacodynamics correlation of vancomycin in pediatric patients, and to propose dose adjustment. This is an observational, cross-sectional study, conducted in a pediatric hospital, over a 1-year period (2016 to 2017). Children of both sexes, aged 2 to 12 years, were included in the study; burn children, and children in renal replacement therapy were excluded. For the pharmacokinetic analysis, two samples of 2mL of whole blood were collected, respecting the 2-hour interval between each withdrawal. Ten pediatric patients with median age of 5.5 years and interquartile range (IQR) of 3.2-9.0 years, median weight of 21kg (IQR: 15.5-24.0kg) and median height of 112.5cm (IQR: 95-133cm), were included. Only one child achieved trough concentrations between 10µg/mL and 15µg/mL. The empirical use of vancomycin in the children studied did not achieve the therapeutic pharmacokinetic/pharmacodynamic target for minimum inhibitory concentration of 1µg/mL.


Warming increases the spread of an invasive thistle.
Global warming and shifted precipitation regimes increasingly affect species abundances and distributions worldwide. Despite a large literature on species' physiological, phenological, growth, and reproductive responses to such climate change, dispersal is rarely examined. Our study aims to test whether the dispersal ability of a non-native, wind-dispersed plant species is affected by climate change, and to quantify the ramifications for future invasion spread rates. We experimentally increased temperature and precipitation in a two-cohort, factorial field study (n = 80). We found an overwhelming warming effect on plant life history: warming not only improved emergence, survival, and reproduction of the thistle Carduus nutans, but also elevated plant height, which increased seed dispersal distances. Using spatial population models, we demonstrate that these empirical warming effects on demographic vital rates, and dispersal parameters, greatly exacerbate spatial spread. Predicted levels of elevated winter precipitation decreased seed production per capitulum, but this only slightly offset the warming effect on spread. Using a spread rate decomposition technique (c*-LTRE), we also found that plant height-mediated changes in dispersal contribute most to increased spread rate under climate change. We found that both dispersal and spread of this wind-dispersed plant species were strongly impacted by climate change. Dispersal responses to climate change can improve, or diminish, a species' ability to track climate change spatially, and should not be overlooked. Methods that combine both demographic and dispersal responses thus will be an invaluable complement to projections of suitable habitat under climate change.


Cardiac and vascular effects of diltiazem, dobutamine and amrinone, drugs used after myocardial revascularization.
Hemodynamic care during postoperative management of myocardial revascularization should include vasorelaxing drugs to insure adequate graft and coronary flow, and stimulation of stroke volume to maintain vascular perfusion pressure. We tested the cardiac (inotropic and lusitropic) and vascular (relaxant) effects of diltiazem (0.1 nM to 0.1 mM), dobutamine (10 microM to 10 mM) and amrinone (10 microM to 1 mM) on isolated rat atria and thoracic aorta, and also on isolated human saphenous vein (HSV) and human mammary artery (HMA). Dobutamine produced a maximal positive inotropic effect (+dF/dt max = 29 +/- 7%) at its ED50 for aortic relaxation (88 +/- 7 microM). Conversely, at their ED50 for aortic relaxation diltiazem depressed myocardial contractility and amrinone did not exhibit myocardial effects. In HSV and HMA contracted with 80 mM potassium, diltiazem and dobutamine (but not amrinone) had a vasorelaxant activity similar to that in rat aorta. Norepinephrine-contracted human vessels were significantly more sensitive than potassium-contracted vessels to the relaxant effect of amrinone (ED50 HMA = 15 +/- 5 microM, ED50 HSV = 72 +/- 31 microM, P < 0.05). We conclude that at concentrations still devoid of myocardial effects dobutamine and amrinone are effective dilators in graft segment vessels and rat aorta contracted by membrane depolarization. If the difference between aortic and myocardial tissue still holds in human tissues, at the appropriate concentrations these drugs should be expected to improve cardiac performance while still contributing to the maintenance of graft patency.


Standardizing ADOS domain scores: separating severity of social affect and restricted and repetitive behaviors.
Standardized Autism Diagnostic Observation Schedule (ADOS) scores provide a measure of autism severity that is less influenced by child characteristics than raw totals (Gotham et al. in Journal of Autism and Developmental Disorders, 39(5), 693-705 2009). However, these scores combine symptoms from the Social Affect (SA) and Restricted and Repetitive Behaviors (RRB) domains. Separate calibrations of each domain would provide a clearer picture of ASD dimensions. The current study separately calibrated raw totals from the ADOS SA and RRB domains. Standardized domain scores were less influenced by child characteristics than raw domain totals, thereby increasing their utility as indicators of Social-Communication and Repetitive Behavior severity. Calibrated domain scores should facilitate efforts to examine trajectories of ASD symptoms and links between neurobiological and behavioral dimensions.


Intravenous arginine-vasopressin in children with vasodilatory shock after cardiac surgery.
Recent investigations at our institution have studied a variety of vasodilatory shock states that are characterized by vasopressin deficiency and pressor hypersensitivity to the exogenous hormone. Our experience in adults prompted the use of arginine-vasopressin (AVP) in a similar group of critically ill children. This report describes our early experience (from February 1997 through April 1998) in 11 profoundly ill infants and children (5 male, 6 female) ages 3 days to 15 years (median, 35 days) treated with AVP for hypotension after cardiac surgery which was refractory to standard cardiopressors. Although underlying heart disease was present (congenital heart defects in 10 and dilated cardiomyopathy in 1), only 2 patients had severely depressed cardiac function as demonstrated by 2D echocardiogram before administration of AVP. All patients were intubated and receiving multiple catecholamine pressors and inotropes, including dobutamine (n=10), epinephrine (n=8), milrinone (n=7), and dopamine (n=4) before receiving AVP. Five patients received AVP intraoperatively immediately after cardiopulmonary bypass, 5 in the intensive care unit within 12 hours of surgery, and 1 on postoperative day 2 for hypotension associated with sepsis. The dose of AVP was adjusted for patient size and ranged from 0.0003 to 0.002 U. kg(-1). min(-1). During the first hour of treatment with AVP, systolic blood pressure rose from 65+/-14 to 87+/-17 mm Hg (P<0. 0001; n=11), and epinephrine administration was decreased in 5 of 8 patients and increased in 1. Plasma AVP levels before treatment were available in 3 patients and demonstrated AVP depletion (median, 4.4 pg/mL; n=3). All 9 children with vasodilatory shock survived their intensive care unit stay. The 2 patients who received AVP in the setting of poor cardiac function died, despite transient improvement in blood pressure. Infants and children with low blood pressure and adequate cardiac function after cardiac surgery respond to the pressor action of exogenous AVP. AVP deficiency may contribute to this hypotensive condition.


Awareness and attitude of diabetic patients about their increased risk for oral diseases.
To assess: 1) awareness of diabetic patients about their increased risk for oral diseases, 2) attitudes of diabetic patients towards maintaining good oral health through oral self-care and regular dental visits and 3) their sources of information on oral health. A self-administered questionnaire was used to assess the main objectives of the study. Two hundred diabetic patients ranging in age from 17 to 78 years old participated in the study. A majority of the participants had type 2 diabetes. The awareness of diabetic patients of their increased risk for oral diseases is low compared to their awareness of systemic diseases. Their attitude towards maintaining good oral health is poor. Of the participants, only 17% brush their teeth twice daily, 61% never use dental floss, and 67% had not visited a dental clinic within the last year. Regarding participants' sources of awareness, 53% learned from a dentist and 30% through other media sources. A significant association (P < 0.05) was found between glycaemic control and oral infections and between duration of diabetes and denture problems. Diabetic patients were found to have little awareness of their increased risk for oral diseases. In order to promote proper oral health and to reduce the risk of oral diseases, health professionals in both the dental and medical fields need to develop programs to educate the public about the oral manifestations of diabetes and its complications for oral health.


Quantum chemistry on quantum computers: quantum simulations of the time evolution of wave functions under the S2 operator and determination of the spin quantum number S.
Quantum computers have an enormous impact on quantum chemical calculations. Approaches to calculate the energies of atoms and molecules on quantum computers by utilizing quantum phase estimation (QPE) and the variational quantum eigensolver (VQE) have been well documented, and dozens of methodological improvements to decrease computational costs and to mitigate errors have been reported until recently. However, the possible methodological implementation of observables on quantum computers such as calculating the spin quantum numbers of arbitrary wave functions, which is a crucial issue in quantum chemistry, has been discussed less. Here, we propose a quantum circuit to simulate the time evolution of wave functions under an S2 operator, exp(-iS2t)|Ψ, and integrate it into the QPE circuit enabling us to determine the spin quantum number of the arbitrary wave functions. We demonstrate that the spin quantum numbers of up to three spins can be determined by only one qubit measurement in QPE.


Antibodies to human thymic epithelium form part of the murine autoreactive repertoire.
Monoclonal antibody (mAb) MR6 recognises a 200 kDa glycoprotein, gp200-MR6, which is expressed at high levels on the surface of human thymic cortical epithelium. In order to produce further mAbs against the gp200-MR6 molecule, mice were immunised with purified human gp200-MR6, hybridomas produced and supernatants screened for MR6-like reactivity on human thymic sections. Surprisingly this conventional hybridoma technique failed to produce stable hybridoma cells producing MR6-like antibodies. However, antibodies with specificities other than MR6-like were obtained. Three such antibodies (1B2, 3A3 and 4B3) were analysed further. Expression of 1B2-antigen, 3A3-antigen and 4B3-antigen was analysed on skin, tonsil and thymic sections, on cultured thymic epithelial cells (TEC), thymocytes and peripheral blood mononuclear cells (PBMC), and found to be expressed by both lymphocytes and epithelial cell populations. Furthermore, the antigens were also expressed on mouse thymic epithelial cells. The regulation of expression of these antigens was analysed following mitogen or cytokine stimulation of PBMC and cultured TEC, respectively. Expression on T cells was clearly affected by mitogens that mimic activation through the T cell receptor and expression on cultured TEC was affected by T cell-derived cytokines. Thus, the shared epithelial-lymphocyte molecules identified in this study may play a role in the cross-talk between the developing thymocytes and their epithelial microenvironment. The production of mAbs with specificities other than that of purified gp200-MR6 indicates that a wide range of B cells with specificity for components of the human thymic microenvironment exist in the normal mouse. These may detect epitopes that are shared with common pathogens to which the animals are exposed. Alternatively, they may be autoreactive B cells that are normally silent in the absence of T cell help. This help may be provided by T cells specific for human gp200-MR6, or nonspecifically by polyclonal activation induced by the adjuvant.


Two divergent members of a tobacco 4-coumarate:coenzyme A ligase (4CL) gene family. cDNA structure, gene inheritance and expression, and properties of recombinant proteins.
Several cDNA clones encoding 4-coumarate:coenzyme A ligase (4CL) were isolated from a tobacco (Nicotiana tabacum) cDNA library and grouped into two classes. Sequencing of one cDNA from each class showed that the clones were similar to other 4CL genes and about 80% identical with each other. Genomic Southern blots using DNA from Nicotiana sylvestris, Nicotiana tomentosiformis, and N. tabacum demonstrated the presence of both classes of 4CL sequences (4CL1 and 4CL2) in the progenitor species and in tobacco. Northern blots indicated that 4CL mRNA transcripts are highest in old stems and higher in the unpigmented corolla tubes than in the pigmented limbs of tobacco flowers. The 4CL genes are developmentally regulated and are wound and methyl jasmonate inducible. The relative abilities of recombinant 4CL1 and 4CL2 proteins to utilize 4-coumarate, ferulate, and caffeate as substrates were similar and comparable with that of 4CL in tobacco stem extracts. Surprisingly, both recombinant 4CL proteins utilized cinnamate as a substrate, an activity not observed in stem extracts. This activity was inhibited by a heat-labile, high-molecular-weight factor found in tobacco stem extracts, suggesting that the substrate specificity of 4CL is, in part, determined by the activity of proteinaceous cellular components.


The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments.
Spironucleus salmonicida causes systemic infections in salmonid fish. It belongs to the group diplomonads, binucleated heterotrophic flagellates adapted to micro-aerobic environments. Recently we identified energy-producing hydrogenosomes in S. salmonicida. Here we present a genome analysis of the fish parasite with a focus on the comparison to the more studied diplomonad Giardia intestinalis. We annotated 8067 protein coding genes in the ∼12.9 Mbp S. salmonicida genome. Unlike G. intestinalis, promoter-like motifs were found upstream of genes which are correlated with gene expression, suggesting a more elaborate transcriptional regulation. S. salmonicida can utilise more carbohydrates as energy sources, has an extended amino acid and sulfur metabolism, and more enzymes involved in scavenging of reactive oxygen species compared to G. intestinalis. Both genomes have large families of cysteine-rich membrane proteins. A cluster analysis indicated large divergence of these families in the two diplomonads. Nevertheless, one of S. salmonicida cysteine-rich proteins was localised to the plasma membrane similar to G. intestinalis variant-surface proteins. We identified S. salmonicida homologs to cyst wall proteins and showed that one of these is functional when expressed in Giardia. This suggests that the fish parasite is transmitted as a cyst between hosts. The extended metabolic repertoire and more extensive gene regulation compared to G. intestinalis suggest that the fish parasite is more adapted to cope with environmental fluctuations. Our genome analyses indicate that S. salmonicida is a well-adapted pathogen that can colonize different sites in the host.


Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation.
Atherosclerosis is one of the major complications of diabetes, which may result from insulin resistance via mitochondrial dysfunction. Although a strong association between insulin resistance and cardiovascular disease has been suggested, it is not clear yet whether stress-inducing factors damage mitochondria and insulin signaling pathway in cardiovascular tissues. We investigated whether stress-induced mitochondrial dysfunction might alter the insulin/Akt signaling pathway in A10 rat vascular smooth muscle cells (VSMC). The treatment of oxidized low density lipoprotein (oxLDL) decreased ATP contents, mitochondrial respiration activity, mRNA expressions of OXPHOS subunits and IRS-1/2 and insulin-mediated phosphorylations of Akt and AMP-activated protein kinase (AMPK). Similarly, dideoxycytidine (ddC), the mtDNA replication inhibitor, or rotenone, OXPHOS complex I inhibitor, inhibited the insulin-mediated pAkt while increased pAMPK regardless of insulin. Reciprocally, an inhibitor of Akt, triciribine (TCN), decreased cellular ATP contents. Overexpression of Akt dominant positive reversed the oxLDL- or ddC-mediated ATP decrease but AMPK activator did not. Akt activation also normalized the aberrant VSMC migration induced by ddC. Defective insulin signaling and mitochondrial function may collectively contribute to developing cardiovascular disease. Akt may be a possible therapeutic target for treating insulin resistance-associated atherosclerosis.


Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission.
Endophilin is a membrane-binding protein with curvature-generating and -sensing properties that participates in clathrin-dependent endocytosis of synaptic vesicle membranes. Endophilin also binds the GTPase dynamin and the phosphoinositide phosphatase synaptojanin and is thought to coordinate constriction of coated pits with membrane fission (via dynamin) and subsequent uncoating (via synaptojanin). We show that although synaptojanin is recruited by endophilin at bud necks before fission, the knockout of all three mouse endophilins results in the accumulation of clathrin-coated vesicles, but not of clathrin-coated pits, at synapses. The absence of endophilin impairs but does not abolish synaptic transmission and results in perinatal lethality, whereas partial endophilin absence causes severe neurological defects, including epilepsy and neurodegeneration. Our data support a model in which endophilin recruitment to coated pit necks, because of its curvature-sensing properties, primes vesicle buds for subsequent uncoating after membrane fission, without being critically required for the fission reaction itself.


Identification of Rgg-regulated exoproteins of Streptococcus pyogenes.
Streptococcus pyogenes secretes many proteins that influence host-pathogen interactions. Despite their importance, relatively little is known about the regulation of these proteins. The rgg gene (also known as ropB) is required for the expression of streptococcal erythrogenic toxin B (SPE B), an extracellular cysteine protease that contributes to virulence. Proteomics was used to determine if rgg regulates the expression of additional exoproteins. Exponential- and stationary-phase culture supernatant proteins made by S. pyogenes NZ131 rgg and NZ131 speB were separated by two-dimensional electrophoresis. Differences were identified in supernatant proteins from both exponential- and stationary-phase cultures, although considerably more differences were detected among stationary-phase supernatant proteins. Forty-two proteins were identified by peptide fingerprinting with matrix-assisted laser desorption mass spectrometry. Mitogenic factor, DNA entry nuclease (open reading frame [ORF 226]), and ORF 953, which has no known function, were more abundant in the culture supernatants of the rgg mutant compared to the speB mutant. ClpB, lysozyme, and autolysin were detected in the culture supernatant of the speB mutant but not the rgg mutant. To determine if Rgg affected protein expression at the transcriptional level, real-time (TaqMan) reverse transcription (RT)-PCR was used to quantitate Rgg-regulated transcripts from NZ131 wild-type and speB and rgg mutant strains. The results obtained with RT-PCR correlated with the proteomic data. We conclude that Rgg regulates the transcription of several genes expressed primarily during the stationary phase of growth.


Fungal infections in immunocompromised travelers.
Immunocompromised patients represent an increasing group of travelers, for business, tourism, and visiting friends and relatives. Those with severe cellular immunodeficiency (advanced human immunodeficiency virus infection and transplant recipients) display the highest risk of fungal infections. International travel is less risky in most other types of immunodeficiency (except those with neutropenia). A systematic visit in a travel clinic for immunocompromised patients traveling to the tropics ensures that the specific risks of acquiring fungal infections (and others) are understood. When immunocompromised hosts return to their area of residence, a nonbacteriologically documented, potentially severe, febrile pneumonia, with or without dissemination signs (skin lesions, cytopenia) should alert for travel-acquired fungal infection, even years after return. Localized subcutaneous nodule may be also ascribed to fungal infection. Finally, infectious diseases physicians should be aware of major clinical patterns of travel-acquired fungal infection, as well as the fungi involved, and risk factors according to the geographical area visited.


Influential Factors on the Evaluation of Adamkiewicz Artery Using a 320-Detector Row Computed Tomography Device.
Understanding the difference of Adamkiewicz artery (AKA) presentation in healthy and diseased subjects, and the influence of atherosclerotic factors prevalent in aortic disease patients, are important for aortic disease therapeutic planning. This study used a 320-detector row computed tomography (CT) device to examine the impact of clinical aspects of AKA identification in individuals with and without aortic disease. Angio-CTs obtained from 115 patients were assessed and the individuals grouped according to the presence or absence of aortic disease. Datasets were analyzed using OsiriX software, and AKA was identified by three-dimensional multiplanar reconstruction. The group without aortic disease (Group A) comprised 32 (52.5%) men and 29 women, with a mean age of 53.7 ± 16.8 years. The group with aortic disease (Group B) comprised 31 (57.4%) men and 23 women, with a mean age of 64.8 ± 11.6 years. AKA was identified in 49 (80.3%) participants of Group A and 23 (42.6%) individuals of Group B (P ≤ 0.0001). In 53 cases (73.6%), AKA originated on the left side. AKA was mainly detected on the left side (73.6%), at the level of T10 to T12 (70%). Tobacco smokers, former smokers, and hypertensive patients had increased odds of having undetected AKA. Using the method described and a state of the art 320-detector row CT device, AKA was detected more frequently among individuals without aortic disease. Thus, aortic disease and atherosclerotic risk factors hindered AKA detection.


Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study.
To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression. Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test. Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU. UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.


Behaviorally inactive doses of mianserin antagonize the suppressant effect of lysergic acid diethylamide on a fixed-ratio operant.
Male Sprague-Dawley rats were trained to respond for food reinforcement on a fixed-ratio 15 schedule. Low, behaviorally inactive, doses of mianserin (0.1-1.0 mg/kg) administered 30 min before the operant session antagonized the behavioral suppression induced by lysergic acid diethylamide (LSD; 50 micrograms/kg) administered immediately before the session. Mianserin (0.5-1.0 mg/kg) also partially antagonized the behavioral suppressant effects of higher doses of LSD. At a dose which suppressed behavior to 70% of control when administered alone, mianserin (10 mg/kg) did not antagonize the behavioral suppression induced by LSD (100-200 micrograms/kg). The data suggest that the suppression of operant behavior produced by mianserin may be the result of nonselective or multiple actions, or possibly the emergence of an LSD-type partial agonist property. Specificity of drug action as an antagonist apparently occurs at the behaviorally inactive, low doses of mianserin which may act through a selective blockade of serotonin receptors stimulated by LSD.


Expression of Human epidermal growth factor receptor 2, Survivin, Enhancer of zeste homolog -2, Cyclooxygenase-2, p53 and p16 molecular markers in Gall bladder carcinoma.
Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging. This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry. Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 - 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ2 = 9.886, P = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ2 = 7.017, P = 0.037 and χ2 = 5.861, P = 0.033) respectively. The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.


Quantification of microcystis in a eutrophic lake by simple DNA extraction and SYBR green real-time PCR.
A simple extraction method and real-time PCR with SYBR-Green I were combined to monitor Microcystis 16S rRNA gene (16S rDNA) concentrations over a wide range. A Fast DNA SPIN Kit (MP Biomedicals) was used to extract rDNA quantitatively. Real-time PCR amplified Microcystis rDNA for quantification with the forward primer Micro229f, which was newly designed by us and was highly specific for Microcystis, and the reverse universal primer 342r. The method developed here can detect Microcystis at concentrations as low as 3 cells mL(-1). The rDNA concentration and cell count were highly correlated in the range from 1.2×10(4) to 1.1×10(6) copies mL(-1) and from 9.5×10(2) to 1.0×10(5) cells mL(-1), respectively, in a canal where Microcystis algal blooms occur annually. The Microcystis rDNA concentration in Lake Kasumigaura was measured by the application of our method to water samples collected monthly from April 2004 to March 2006. Microcystis was not detected by microscopy from January to June 2005, except in May, but our method detected 1.0×10(3) to 1.0×10(4) copies mL(-1) of Microcystis rDNA during this period. This result clearly showed that our method is useful for clarifying the annual fluctuation in Microcystis concentration, especially when concentrations are low.


Acoustic Radiation Force Optical Coherence Elastography of Corneal Tissue.
We report on a real-time acoustic radiation force optical coherence elastography (ARF-OCE) system to map the relative elasticity of corneal tissue. A modulated ARF is used as excitation to vibrate the cornea while OCE serves as detection of tissue response. To show feasibility of detecting mechanical contrast using this method, we performed tissue-equivalent agarose phantom studies with inclusions of a different stiffness. We obtained 3-D elastograms of a healthy cornea and a highly cross-linked cornea. Finally we induced a stiffness change on a small portion of a cornea and observed the differences in displacement.


Elucidating the Drug Release from Metal-Organic Framework Nanocomposites via In Situ Synchrotron Microspectroscopy and Theoretical Modeling.
Nanocomposites comprising metal-organic frameworks (MOFs) embedded in a polymeric matrix are promising carriers for drug delivery applications. While understanding the chemical and physical transformations of MOFs during the release of confined drug molecules is challenging, this is central to devising better ways for controlled release of therapeutic agents. Herein, we demonstrate the efficacy of synchrotron microspectroscopy to track the in situ release of 5-fluorouracil (5-FU) anticancer drug molecules from a drug@MOF/polymer composite (5-FU@HKUST-1/polyurethane). Using experimental time-resolved infrared spectra jointly with newly developed density functional theory calculations, we reveal the detailed dynamics of vibrational motions underpinning the dissociation of 5-FU bound to the framework of HKUST-1 upon water exposure. We discover that HKUST-1 creates hydrophilic channels within the hydrophobic polyurethane matrix hence helping to tune drug release rate. The synergy between a hydrophilic MOF with a hydrophobic polymer can be harnessed to engineer a tunable nanocomposite that alleviates the unwanted burst effect commonly encountered in drug delivery.


Transitional care cut hospital readmissions for North Carolina Medicaid patients with complex chronic conditions.
Recurrent hospitalizations represent a substantial and often preventable human and financial burden in the United States. In 2008 North Carolina initiated a statewide population-based transitional care initiative to prevent recurrent hospitalizations among high-risk Medicaid recipients with complex chronic medical conditions. In a study of patients hospitalized during 2010-11, we found that those who received transitional care were 20 percent less likely to experience a readmission during the subsequent year, compared to clinically similar patients who received usual care. Benefits of the intervention were greatest among patients with the highest readmission risk. One readmission was averted for every six patients who received transitional care services and one for every three of the highest-risk patients. This study suggests that locally embedded, targeted care coordination interventions can effectively reduce hospitalizations for high-risk populations.


[Apoptosis-inducing effect of quercetin and kaempferol on human HL-60 cells and its mechanism].
The purpose of this study was to explore the anti-leukemia effect of quercetin and kaempferol and its mechanism. The HL-60 cells were used as the leukemia models. The inhibitory effects of quercetin and kaempferol on growth of HL-60 cells was assessed by MTT assay. The effect of quercetin and kaempferol on cell cycle in HL-60 cells was detected by flow cytometry. The cytotoxic effect of these 2 drugs was analysed by single cell electrophoresis assay. Western blot analysis was used to study the apoptotic mechanism of HL-60 cells. The results showed that the quercetin and kaempferol had a significant anti-leukemia effect in vitro. The proliferation of HL-60 cells was significantly inhibited in dose-and time-dependent manners after treating with quercetin (r = 0.77) and kaempferol (r = 0.76) respectively, and the cytotoxicity of quercetin was superior to that of kaempferol. The quercetin and kaempferol induced G(2)/M arrest and apoptosis of HL-60 cells. The quercetin and kaempferol could down-regulate the survivin expression. It is concluded that the quercetin and kaempferol have significant anti-leukemia effect in vitro. Furthermore the apoptosis-inducing effect of quercetin is stronger than that of kaempferol, both of which induce apoptosis of HL-60 cells through depressing cell growth, arresting cell cycle and inhibiting expression of survivin.


EPA Consensus Project Paper: Shifting from the "Analogic Virtual Patient" to the "Digital Virtual Patient" in Prosthodontics. A Scoping Review.
To determine whether the use of single or combined mechanical and virtual articulators, as well as facebows, jaw motion trackers, face scanners, and related devices, actually improve the efficacy of the prosthesis obtained in terms of lifespan and patient-related outcomes. To coin the terms Analogic and Digital Virtual Patients (AVP and DVP) as an attempt to analyze, clarify and synthesize terminology and workflows related to previously so-called devices. A scoping review was accomplished involving different databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR) checklist and JBI guidance were followed to extract data regarding the Population, Context and Concept established. Available literature on the efficacy of using devices and techniques related to both AVP and DVP workflows showed arguable study designs, great heterogeneity, and questionable quality. The terms AVP and DVP have been coined as a first step to clarify and simplify concepts and workflows related to the use of both mechanical and virtual articulators, as well as facebows, or facial and intraoral scanners, among others. This scoping review cannot claim that an AVP approach leads to more effective and efficient prosthetic restorations.


Manipulation of Karyotype in Caenorhabditis elegans Reveals Multiple Inputs Driving Pairwise Chromosome Synapsis During Meiosis.
Meiotic chromosome segregation requires pairwise association between homologs, stabilized by the synaptonemal complex (SC). Here, we investigate factors contributing to pairwise synapsis by investigating meiosis in polyploid worms. We devised a strategy, based on transient inhibition of cohesin function, to generate polyploid derivatives of virtually any Caenorhabditis elegans strain. We exploited this strategy to investigate the contribution of recombination to pairwise synapsis in tetraploid and triploid worms. In otherwise wild-type polyploids, chromosomes first sort into homolog groups, then multipartner interactions mature into exclusive pairwise associations. Pairwise synapsis associations still form in recombination-deficient tetraploids, confirming a propensity for synapsis to occur in a strictly pairwise manner. However, the transition from multipartner to pairwise association was perturbed in recombination-deficient triploids, implying a role for recombination in promoting this transition when three partners compete for synapsis. To evaluate the basis of synapsis partner preference, we generated polyploid worms heterozygous for normal sequence and rearranged chromosomes sharing the same pairing center (PC). Tetraploid worms had no detectable preference for identical partners, indicating that PC-adjacent homology drives partner choice in this context. In contrast, triploid worms exhibited a clear preference for identical partners, indicating that homology outside the PC region can influence partner choice. Together, our findings, suggest a two-phase model for C. elegans synapsis: an early phase, in which initial synapsis interactions are driven primarily by recombination-independent assessment of homology near PCs and by a propensity for pairwise SC assembly, and a later phase in which mature synaptic interactions are promoted by recombination.


A cross-national study on the multidimensional characteristics of the five-item psychological demands scale of the Job Content Questionnaire.
The five-item psychological demands scale of the Job Content Questionnaire (JCQ) has been assumed to be one-dimensional in practice. To examine whether the scale has sufficient internal consistency and external validity to be treated as a single scale, using the cross-national JCQ datasets from the United States, Korea, and Japan. Exploratory factor analyses with 22 JCQ items, confirmatory factor analyses with the five psychological demands items, and correlations analyses with mental health indexes. Generally, exploratory factor analyses displayed the predicted demand/control/support structure with three and four factors extracted. However, at more detailed levels of exploratory and confirmatory factor analyses, the demands scale showed clear evidence of multi-factor structure. The correlations of items and subscales of the demands scale with mental health indexes were similar to those of the full scale in the Korean and Japanese datasets, but not in the U.S. data. In 4 out of 16 sub-samples of the U.S. data, several significant correlations of the components of the demands scale with job dissatisfaction and life dissatisfaction were obscured by the full scale. The multidimensionality of the psychological demands scale should be considered in psychometric analysis and interpretation, occupational epidemiologic studies, and future scale extension.


Combining Healthcare-Based and Participatory Approaches to Surveillance: Trends in Diarrheal and Respiratory Conditions Collected by a Mobile Phone System by Community Health Workers in Rural Nepal.
Surveillance systems are increasingly relying upon community-based or crowd-sourced data to complement traditional facilities-based data sources. Data collected by community health workers during the routine course of care could combine the early warning power of community-based data collection with the predictability and diagnostic regularity of facility data. These data could inform public health responses to epidemics and spatially-clustered endemic diseases. Here, we analyze data collected on a daily basis by community health workers during the routine course of clinical care in rural Nepal. We evaluate if such community-based surveillance systems can capture temporal trends in diarrheal diseases and acute respiratory infections. During the course of their clinical activities from January to December 2013, community health workers recorded healthcare encounters using mobile phones. In parallel, we accessed condition-specific admissions from 2011-2013 in the hospital from which the community health program was based. We compared diarrhea and acute respiratory infection rates from both the hospital and the community, and assigned three categories of local disease activity (low, medium, and high) to each week in each village cluster with categories determined by tertiles. We compared condition-specific mean hospital rates across categories using ANOVA to assess concordance between hospital and community-collected data. There were 2,710 cases of diarrhea and 373 cases of acute respiratory infection reported by community health workers during the one-year study period. At the hospital, the average weekly incidence of diarrhea and acute respiratory infections over the three-year period was 1.8 and 3.9 cases respectively per 1,000 people in each village cluster. In the community, the average weekly rate of diarrhea and acute respiratory infections was 2.7 and 0.5 cases respectively per 1,000 people. Both diarrhea and acute respiratory infections exhibited significant differences between the three categories of disease rate burden (diarrhea p = 0.009, acute respiratory infection p = 0.001) when comparing community health worker-collected rates to hospital rates. Community-level data on diarrhea and acute respiratory infections modestly correlated with hospital data for the same condition in each village each week. Our experience suggests that community health worker-collected data on mobile phones may be a feasible adjunct to other community- and healthcare-related data sources for surveillance of such conditions. Such systems are vitally needed in resource-limited settings like rural Nepal.


Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of β -Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity.
Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2-dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of β -glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of β -glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of β -glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level.


Anesthetic management of catheter-based patent ductus arteriosus closure in neonates weighing <3 kg: A Retrospective Observational Study.
The patent ductus arteriosus is a cardiac lesion commonly found in premature neonates. Though surgical closure via thoracotomy is the most definitive treatment option, it is associated with significant morbidity. New catheter-based closure options offer a potentially safer alternative treatment, even in premature neonates. However, no literature reports the anesthetic techniques, challenges, and risks associated with this procedure in this population. This study documents the anesthetic challenges and potential complications associated with the management of catheter-based closure of the ductus arteriosus in neonates under 3 kg. This single-center, retrospective study examined patients who underwent catheter-based ductus arteriosus closure between August 2015 and February 2019. A clinical protocol for anesthetic management of these patients was utilized throughout the study period. Clinical outcomes considered were new hemodynamic instability or vasoactive medication requirements, hypothermia, prolonged intubation (>3 days postoperatively), postprocedure acute kidney injury, perioperative red blood cell transfusion, and accidental extubation. Seventy-six neonates underwent 78 procedures. No patient developed perioperative hemodynamic instability, vasoactive medication requirements, or acute kidney injury. Four patients (5%) required red blood cell transfusion, two (3%) became hypothermic, and one (1%) was accidentally extubated. Closure was achieved in 73 patients (96%) on the first attempt. However, 17 patients (40%) required prolonged periods of mechanical ventilation following the procedure. Despite multiple clinical and logistical challenges, anesthetic risk associated with catheter-based PDA closure in small neonates can be effectively managed through standardized and multidisciplinary care.


Studies on cultured and uncultured microbiota of wild culex quinquefasciatus mosquito midgut based on 16s ribosomal RNA gene analysis.
To describe the midgut microbial diversity and the candidate bacteria for the genetic manipulation for the generation of transgenic mosquitoes refractory to transmission of diseases, the microbiota of wild Culex quinquefasciatus mosquito midgut was studied using a conventional culture technique and analysis of a 16S ribosomal RNA (rRNA) gene sequence library. The culturable microbiota was identified as Acinetobacter junii, Ac. calcoaceticus, Aeromonas culicicola, Bacillus thuringiensis, Microbacterium oxydans, Pantoea agglomerans, Pseudomonas aeruginosa, Staphylococcus epidermidis, Stenotrophomonas maltophila and an unidentified bacterium from the host Drosophila paulistorium. The 16S rRNA gene library was composed of 46% unidentified and uncultured bacteria, 41% Acinetobacter spp., and 13% Lactococcus spp. The coverage calculated for the 150 clones was 83.3%. Thus, the probability of the next cloned sequence falling in a novel operational taxonomic unit (not yet observed) was 16.7%. The majority of the cultured isolates and the 16S rRNA gene library clones belonged to the gamma-proteobacteria class. Most of the bacteria have been previously reported to inhabit the midgut of different mosquito species. Therefore, the results of this study indicate that different mosquito species harbor common representatives of the microbiota that may be the potential candidates for genetic manipulation to control the disease transmission capabilities of the host.


Parsimonious Model for Simulating Total Mercury and Methylmercury in Boreal Streams Based on Riparian Flow Paths and Seasonality.
The complexity of mercury (Hg) biogeochemistry has made it difficult to model surface water concentrations of both total Hg (THg) and especially methylmercury (MeHg), the species of Hg having the highest potential for bioaccumulation. To simulate THg and MeHg variation in low-order streams, we have adapted a conceptual modeling framework where a continuum of lateral flows through riparian soils determines streamflow concentrations. The model was applied to seven forest catchments located in two boreal regions in Sweden spanning a range of climatic, soil, and forest management conditions. Discharge, and simulated riparian soil water concentrations profiles, represented by two calibrated parameters, were able to explain much of the variability of THg and MeHg concentrations in the streams issuing from the catchments (Nash Sutcliffe (NS) up to 0.54 for THg and 0.58 for MeHg). Model performance for all catchments was improved (NS up to 0.76 for THg and 0.85 for MeHg) by adding two to four parameters to represent seasonality in riparian soil water THg and MeHg concentrations profiles. These results are consistent with the hypothesis that riparian flow-pathways and seasonality in riparian soil concentrations are the major controls on temporal variation of THg and MeHg concentrations in low-order streams.


Caregiver distress, shared traumatic exposure, and child adjustment among area youth following the 2013 Boston Marathon bombing.
Disasters are associated with myriad negative outcomes in youth, including posttraumatic stress disorder and related psychopathology. Prior work suggests links between caregiver distress and child mental health outcomes following community traumas, but the extent to which caregiver distress is directly linked to post-disaster child functioning, or whether such associations may simply be due to shared traumatic exposure, remains unclear. The current study examined relationships among caregiver distress, caregiver-child shared traumatic exposure, and child outcomes in Boston-area families (N=460) during the six months following the 2013 Boston Marathon bombing. Parents completed surveys about their and their child׳s potentially traumatic experiences during the bombing and subsequent manhunt. Post-attack caregiver distress and child psychological functioning were also assessed. After accounting for caregiver-child shared traumatic exposure, significant associations were retained between caregiver distress and child functioning across several domains. Furthermore, after accounting for caregiver traumatic exposure, caregiver distress moderated relationships between child traumatic exposure and child posttraumatic stress and conduct problems, such that associations between child traumatic exposure and child posttraumatic stress and conduct problems were particularly strong among children of highly distressed caregivers. The cross-sectional design did not permit evaluations across time, and population-based methods were not applied. Findings clarify links between caregiver distress and child psychopathology in the aftermath of disaster and can inform optimal allocation of clinical resources targeting disaster-affected youth and their families.


Duplications of the bulbous urethra: clinicoradiologic findings and therapeutic options.
We evaluated the clinical and radiological aspects of isolated duplications of the bulbous urethra and assessed the results of surgical treatment. The experience with 11 male patients presenting with duplications of the bulbous urethra is reported. The duplications were incomplete in 7 cases and complete in 4, the accessory channel was ventral in 8 patients and dorsal in 3. The presenting symptoms were seldom indicative of the condition. Surgical treatment was performed in 10 cases and consisted in transurethral resection of the septum between the two channels in 2 patients, one-stage urethroplasty in 6 and two-stage urethroplasty in 2. With a follow-up ranging between 1 and 4 years the results were considered satisfactory in 4 cases and excellent in 6. Duplications of the bulbous urethra deserve careful evaluation of the cost-benefit ratio when surgical treatment is considered. The goal of reconstructive surgery, which can be open or transurethral, should be a functional urethral channel.


Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression.
We have characterized an inhibitory RNA element in the human immunodeficiency virus type 1 (HIV-1) gag coding sequence that prevents gag expression. The inhibition exerted by this element could be overcome by the presence of the Rev-responsive element in cis and of Rev protein in trans. To understand the mechanism of function, we inactivated the inhibitory element by mutagenesis while maintaining an intact gag coding region. A constitutive high level of Rev-independent gag expression was achieved only after the introduction of 28 point mutations over a large region of 270 nucleotides within the gag coding region. To our knowledge, this is the first demonstration of inactivation of a negative RNA element within a coding region without alteration of the expressed protein. Elimination of the inhibitory element in the p17gag region, named INS-1, offered the opportunity to detect a second inhibitory element in the gag-pol region. The presence of either INS element is sufficient to inhibit gag expression, demonstrating that multiple INS elements acting independently can inhibit HIV RNA expression. Expression of gag from Rous sarcoma virus, a retrovirus that does not require Rev-like regulatory proteins, revealed that the Rous sarcoma virus p19gag region does not contain inhibitory elements. These results demonstrate the presence of a strong inhibitory element acting at the level of mRNA and provide a general method for the removal of such elements from mRNA coding regions. The inhibitory element functions in the absence of any HIV-1 proteins, suggesting that cellular factors are responsible for this inhibition.


Complementary feeding adequacy in relation to nutritional status among early weaned breastfed children who are born to HIV-infected mothers: ANRS 1201/1202 Ditrame Plus, Abidjan, Cote d'Ivoire.
In high HIV prevalence resource-constrained settings, exclusive breastfeeding with early cessation is one of the conceivable interventions aimed at the prevention of HIV through breast milk. Nevertheless, this intervention has potential adverse effects, such as the inappropriateness of complementary feeding to take over breast milk. The purpose of our study first was to describe the nature and the ages of introduction of complementary feeding among early weaned breastfed infants up to their first birthday and second was to assess the nutritional adequacy of these complementary foods by creating a child feeding index and to investigate its association with child nutritional status. A prospective cohort study in Abidjan, Côte d'Ivoire, was conducted in HIV-infected pregnant women who were willing to breastfeed and had received a perinatal antiretroviral prophylaxis. They were requested to practice exclusive breastfeeding and initiate early cessation of breastfeeding from the fourth month to reduce breast milk HIV transmission. Nature and ages of introductory complementary feeding were described in infants up to their first birthday by longitudinal compilation of 24-hour and 7-day recall histories. These recalls were done weekly until 6 weeks of age, monthly until 9 months of age, and then quarterly. We created an index to synthesize the nutritional adequacy of infant feeding practices (in terms of quality of the source of milk, dietary diversity, food, and meal frequencies) ranging from 0 to 12. The association of this feeding index with growth outcomes in children was investigated. Among the 262 breastfed children included, complete cessation of breastfeeding occurred in 77% by their first birthday, with a median duration of 4 months. Most of the complementary foods were introduced within the seventh month of life, except for infant food and infant formula that were introduced at age 4 months. The feeding index was relatively low (5 of 12) at age 6 months, mainly as a result of insufficient dietary diversity, but was improved in the next 6 months (8.5 of 12 at 12 months of age). Inadequate complementary feeding at age 6 months was associated with impaired growth during the next 12 months, with a 37% increased probability of stunting. Adequate feeding practices around the weaning period are crucial to achieving optimal child growth. HIV-infected women should turn to early cessation of breastfeeding only when they are counseled properly to provide adequate complementary feeding to take over breast milk. Our child feeding index could contribute to the assessment of the nutritional adequacy of complementary feeding around the weaning period and therefore help to detect children who are at risk for malnutrition.