Risk factors associated with Hepatitis C among female substance users enrolled in community-based HIV prevention studies

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is one of the most frequent chronic blood-borne infections in the United States. The epidemiology of HCV transmission is not completely understood, particularly in women and minorities.</p> <p>Findings</p> <p>We examined the HCV associated risk factors in substance abusing females involved in National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA) funded HIV prevention studies of street recruited women. As a part of the 12 month follow-up, participants were interviewed about substance use and sexual risk behaviors, including drug implement sharing practices, tattoos, body piercing and blood transfusions and the sharing of personal hygiene equipment including tweezers, toothbrushes and razors. Urine and blood testing for HCV antibody (Ab), HIV and sexually transmitted diseases (STDs) was conducted at the time of assessment.</p> <p>Among 782 predominantly African American women, 162 (21%) tested positive for HCV Ab. Older age (p < 0.001), history of injection drug use (p < 0.001), lifetime crack cocaine use (p = 0.004) and having a tattoo (p = 0.01) were significantly associated with HCV Ab positivity. Other risk factors previously reported in association with HCV Ab positivity such as sexual risk behaviors were not significantly associated with the presence of a positive HCV Ab.</p> <p>Conclusions</p> <p>This large community based sample of predominantly African American substance abusing women showed high prevalence of HCV Ab positivity and low awareness of their HCV serostatus. Our study demonstrated that in addition to intravenous drug use (IDU), other factors were significantly associated with HCV Ab positivity such as having a tattoo and a lifetime history of crack use. Other potential routes of HCV transmission should be further studied among high risk female populations.</p

Joint MiRNA/mRNA expression profiling reveals rhanges consistent with development of dysfunctional corpus luteum after weight gain

<div><p>Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (<i>Chlorocebus aethiops</i>) during weight gain. 10 months of high-fat, high-fructose diet (HFHF) resulted in a 20% weight gain for HFHF animals vs. 2% for controls (p = 0.03) and a 66% increase in percent fat mass for HFHF group. Ovulation was confirmed at baseline and after intervention in all animals. CL were collected on luteal day 7–9 based on follicular phase estradiol peak. 432 mRNAs and 9 miRNAs were differentially expressed in response to HFHF diet. Specifically, miR-28, miR-26, and let-7b previously shown to inhibit sex steroid production in human granulosa cells, were up-regulated. Using integrated miRNA and gene expression analysis, we demonstrated changes in 52 coordinately regulated mRNA targets corresponding to opposite changes in miRNA. Specifically, 2 targets of miR-28 and 10 targets of miR-26 were down-regulated, including genes linked to follicular development, steroidogenesis, granulosa cell proliferation and survival. To the best of our knowledge, this is the first report of dietary-induced responses of the ovulating ovary to developing adiposity. The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women. MiRNAs may represent novel biomarkers of obesity-related subfertility and potential new avenues for therapeutic intervention.</p></div

A survey of cost-sensitive decision tree induction algorithms

The past decade has seen a significant interest on the problem of inducing decision trees that take account of costs of misclassification and costs of acquiring the features used for decision making. This survey identifies over 50 algorithms including approaches that are direct adaptations of accuracy based methods, use genetic algorithms, use anytime methods and utilize boosting and bagging. The survey brings together these different studies and novel approaches to cost-sensitive decision tree learning, provides a useful taxonomy, a historical timeline of how the field has developed and should provide a useful reference point for future research in this field

Using surveillance data to monitor entry into care of newly diagnosed HIV-infected persons: San Francisco, 2006–2007

<p>Abstract</p> <p>Background</p> <p>Linkage to care after HIV diagnosis is associated with both clinical and public health benefits. However, ensuring and monitoring linkage to care by public health departments has proved to be a difficult task. Here, we report the usefulness of routine monitoring of CD4 T cell counts and plasma HIV viral load as measures of entry into care after HIV diagnosis.</p> <p>Methods</p> <p>Since July 1, 2006, the San Francisco Department of Public Health (SFDPH) incorporated monitoring initial primary care visit into standard HIV public health investigation for newly diagnosed HIV-infected patients in select clinics. Entry into care was defined as having at least one visit to a primary HIV care provider after the initial diagnosis of HIV infection. Investigators collected reports from patients, medical providers, laboratories and reviewed medical records to determine the date of the initial health care visit after HIV diagnosis. We identified factors associated with increased likelihood of entering care after HIV diagnosis.</p> <p>Results</p> <p>One -hundred and sixty new HIV-infected cases were diagnosed between July 1, 2006 and June 30, 2007. Routine surveillance methods found that 101 of those cases entered HIV medical care and monitoring of CD4 T cell counts and plasma HIV viral load confirmed entry to care of 25 more cases, representing a 25% increase over routine data collection methods. We found that being interviewed by a public health investigator was associated with higher odds of entry into care after HIV diagnosis (OR 18.86 [1.83–194.80], p = .001) compared to cases not interviewed. Also, HIV diagnosis at the San Francisco county hospital versus diagnosis at the county municipal STD clinic was associated with higher odds of entry into care (OR 101.71 [5.29–1952.05], p < .001).</p> <p>Conclusion</p> <p>The time from HIV diagnosis to initial CD4 T cell count, CD4 T cell value and HIV viral load testing may be appropriate surveillance measures for evaluating entry into care, as well as performance outcomes for local public health departments' HIV testing programs. Case investigation performed by the public health department or case management by clinic staff was associated with increased and shorter time to entry into HIV medical care.</p

Vapour pressure deficit modulates hydraulic function and structure of tropical rainforests under nonlimiting soil water supply

Atmospheric conditions are expected to become warmer and drier in the future, but little is known about how evaporative demand influences forest structure and function independently from soil moisture availability, and how fast-response variables (such as canopy water potential and stomatal conductance) may mediate longer-term changes in forest structure and function in response to climate change. We used two tropical rainforest sites with different temperatures and vapour pressure deficits (VPD), but nonlimiting soil water supply, to assess the impact of evaporative demand on ecophysiological function and forest structure. Common species between sites allowed us to test the extent to which species composition, relative abundance and intraspecific variability contributed to site-level differences. The highest VPD site had lower midday canopy water potentials, canopy conductance (gc), annual transpiration, forest stature, and biomass, while the transpiration rate was less sensitive to changes in VPD; it also had different height–diameter allometry (accounting for 51% of the difference in biomass between sites) and higher plot-level wood density. Our findings suggest that increases in VPD, even in the absence of soil water limitation, influence fast-response variables, such as canopy water potentials and gc, potentially leading to longer-term changes in forest stature resulting in reductions in biomass

A Lectin HPLC Method to Enrich Selectively-glycosylated Peptides from Complex Biological Samples

Glycans are an important class of post-translational modifications. Typically found on secreted and extracellular molecules, glycan structures signal the internal status of the cell. Glycans on tumor cells tend to have abundant sialic acid and fucose moieties. We propose that these cancer-associated glycan variants be exploited for biomarker development aimed at diagnosing early-stage disease. Accordingly, we developed a mass spectrometry-based workflow that incorporates chromatography on affinity matrices formed from lectins, proteins that bind specific glycan structures. The lectins Sambucus nigra (SNA) and Aleuria aurantia (AAL), which bind sialic acid and fucose, respectively, were covalently coupled to POROS beads (Applied Biosystems) and packed into PEEK columns for high pressure liquid chromatography (HPLC). Briefly, plasma was depleted of the fourteen most abundant proteins using a multiple affinity removal system (MARS-14; Agilent). Depleted plasma was trypsin-digested and separated into flow-through and bound fractions by SNA or AAL HPLC. The fractions were treated with PNGaseF to remove N-linked glycans, and analyzed by LC-MS/MS on a QStar Elite. Data were analyzed using Mascot software. The experimental design included positive controls—fucosylated and sialylated human lactoferrin glycopeptides—and negative controls—high mannose glycopeptides from Saccharomyces cerevisiae—that were used to monitor the specificity of lectin capture. Key features of this workflow include the reproducibility derived from the HPLC format, the positive identification of the captured and PNGaseF-treated glycopeptides from their deamidated Asn-Xxx-Ser/Thr motifs, and quality assessment using glycoprotein standards. Protocol optimization also included determining the appropriate ratio of starting material to column capacity, identifying the most efficient capture and elution buffers, and monitoring the PNGaseF-treatment to ensure full deglycosylation. Future directions include using this workflow to perform mass spectrometry-based discovery experiments on plasma from breast cancer patients and control individuals

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma

BackgroundWe sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene‐specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA).MethodsThe tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene‐specific alteration frequencies were compared (Chi‐Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform.ResultsPersistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53.ConclusionsOur results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/1/hed25444.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/2/hed25444_am.pd

Neurophysiology

Contains reports on twenty research projects.Bell Laboratories (Grant)National Institutes of Health (Grant 5 R01 EY01149-03S2)National Institutes of Health (Grant 5 TO1 EY00090-04)National Institutes of Health (Grant 5 RO1 NS12307-03)National Institutes of Health (Grant K04 NS00010)National Multiple Sclerosis Society (Grant RG-1133-A-1)Health Sciences Fund (Grant 78-10