Injection drug use, HIV/HCV, and related services in nonurban areas of the United States: A systematic review

Background—Injection drug use (IDU) in nonurban areas of the United States is a growing public health concern, but there has been no comprehensive assessment of existing research on injection-related HIV and hepatitis C (HCV) in nonurban communities. We conducted a systematic review to assess the current literature and identify knowledge gaps. Methods—We systematically searched six databases for relevant articles published between January 1990 and June 2016 and screened, extracted, and analyzed the resulting data. Studies were included if they reported original findings from the nonurban U.S. related to 1) IDU and its role in HIV/HCV transmission, and/or 2) HIV/HCV services for people who inject drugs (PWID). Results—Of 2,330 studies, 34 from 24 unique research projects in 17 states met inclusion criteria. Despite increasing HCV and high vulnerability to injection-related HIV outbreaks in nonurban areas, only three studies since 2010 recruited and tested PWID for HIV/HCV. Twelve reported on sharing injection equipment but used varying definitions of sharing, and only eight examined correlates of injection risk. Nine studies on syringe access suggest limited access through syringe exchange programs and pharmacies. Only two studies addressed HCV testing, none addressed HIV testing, and three examined behavioral or other interventions. Conclusions—Despite growing concern regarding nonurban IDU there are few studies of HIV/HCV and related services for PWID, and the existing literature covers a very limited geographical area. Current research provides minimal insights into any unique factors that influence injection risk and HIV/HCV service provision and utilization among nonurban PWID

Molecular characterization of ‘Candidatus Phytoplasma prunorum’ in Cacopsilla pruni insect vector

Recent investigations on molecular characterization of the ‘Candidatus Phytoplasma prunorum’ (16SrX-B subgroup), causal agent of the European Stone Fruit Yellows (ESFY) syndrome, on the non ribosomal tuf gene resulted in the finding of two groups of isolates, named ‘type a’ and ‘type b’, both with a distinctive geographical distribution in Italian stone fruit growing areas (Ferretti et al., 2007 and 2008). Considering the role of Cacopsylla pruni (Scopoli) in the epidemiological cycle of the disease, the presence of the two groups of isolates has also been investigated in infected psyllid individuals from different Italian areas. Both types have been identified in C. pruni specimens collected on apricot, plum and wild Prunus species, confirming the geographical distribution and the percentages of spread of the two isolates.Keywords: ESFY, phytoplasma, characterization, tuf gene, insect vecto

Physiological Adjustments to Stress Measures Following Massage Therapy: A Review of the Literature

Use of massage therapy by the general public has increased substantially in recent years. In light of the popularity of massage therapy for stress reduction, a comprehensive review of the peer-reviewed literature is important to summarize the effectiveness of this modality on stress-reactive physiological measures. On-line databases were searched for articles relevant to both massage therapy and stress. Articles were included in this review if (i) the massage therapy account consisted of manipulation of soft tissues and was conducted by a trained therapist, and (ii) a dependent measure to evaluate physiological stress was reported. Hormonal and physical parameters are reviewed. A total of 25 studies met all inclusion criteria. A majority of studies employed a 20–30 min massage administered twice-weekly over 5 weeks with evaluations conducted pre-post an individual session (single treatment) or following a series of sessions (multiple treatments). Single treatment reductions in salivary cortisol and heart rate were consistently noted. A sustained reduction for these measures was not supported in the literature, although the single-treatment effect was repeatable within a study. To date, the research data is insufficient to make definitive statements regarding the multiple treatment effect of massage therapy on urinary cortisol or catecholamines, but some evidence for a positive effect on diastolic blood pressure has been documented. While significant improvement has been demonstrated following massage therapy, the general research body on this topic lacks the necessary scientific rigor to provide a definitive understanding of the effect massage therapy has on many physiological variables associated with stress

Reconciling Incongruous Qualitative and Quantitative Findings in Mixed Methods Research: Exemplars from Research with Drug Using Populations

Mixed methods research is increasingly being promoted in the health sciences as a way to gain more comprehensive understandings of how social processes and individual behaviours shape human health. Mixed methods research most commonly combines qualitative and quantitative data collection and analysis strategies. Often, integrating findings from multiple methods is assumed to confirm or validate the findings from one method with the findings from another, seeking convergence or agreement between methods. Cases in which findings from different methods are congruous are generally thought of as ideal, whilst conflicting findings may, at first glance, appear problematic. However, the latter situation provides the opportunity for a process through which apparently discordant results are reconciled, potentially leading to new emergent understandings of complex social phenomena. This paper presents three case studies drawn from the authors’ research on HIV risk amongst injection drug users in which mixed methods studies yielded apparently discrepant results. We use these case studies (involving injection drug users [IDUs] using a Needle/Syringe Exchange Program in Los Angeles, CA, USA; IDUs seeking to purchase needle/syringes at pharmacies in Tijuana, Mexico; and young street-based IDUs in San Francisco, CA, USA) to identify challenges associated with integrating findings from mixed methods projects, summarize lessons learned, and make recommendations for how to more successfully anticipate and manage the integration of findings. Despite the challenges inherent in reconciling apparently conflicting findings from qualitative and quantitative approaches, in keeping with others who have argued in favour of integrating mixed methods findings, we contend that such an undertaking has the potential to yield benefits that emerge only through the struggle to reconcile discrepant results and may provide a sum that is greater than the individual qualitative and quantitative parts

Identification of a novel plasmid lineage associated with the dissemination of metallo-β-lactamase genes among pseudomonads

Acquisition of metallo-\u3b2-lactamases (MBLs) represents one of most relevant resistance mechanisms to all \u3b2-lactams, including carbapenems, ceftolozane and available \u3b2-lactamase inhibitors, in Pseudomonas spp. VIM-type enzymes are the most common acquired MBLs in Pseudomonas aeruginosa and, to a lesser extent, in other Pseudomonas species. Little is known about the acquisition dynamics of these determinants, that are usually carried on integrons embedded into chromosomal mobile genetic elements. To date, few MBL-encoding plasmids have been described in Pseudomonas spp., and their diversity and role in the dissemination of these MBLs remains largely unknown. Here we report on the genetic features of the VIM-1encoding plasmid pMOS94 from P. mosselii AM/94, the earliest known VIM-1-producing strain, and of related elements involved in dissemination of MBL. Results of plasmid DNA sequencing showed that pMOS94 had a modular organization, consisting of backbone modules associated with replication, transfer and antibiotic resistance. Plasmid pMOS94, although not typable according to the PBRT scheme, was classifiable either in MOBF11 or MPFT plasmid families. The resistance region included the class I integron In70, carrying blaVIM-1, in turn embedded in a defective Tn402-like transposon. Comparison with pMOS94-like elements led to the identification of a defined plasmid lineage circulating in different Pseudomonas spp. of clinical and environmental origin and spreading different MBL-encoding genes, including blaIMP-63, blaBIM, and blaVIM-type determinants. Genetic analysis revealed that this plasmid lineage likely shared a common ancestor and had evolved through the acquisition and recombination of different mobile elements, including the MBL-encoding transposons. Our findings provide new insights about the genetic diversity of MBL-encoding plasmids circulating among Pseudomonas spp., potentially useful for molecular epidemiology purposes, and revealed the existence and persistence of a successful plasmid lineage over a wide spatio-temporal interval, spanning over five different countries among two continents and over 20-years

Not sold here: limited access to legally available syringes at pharmacies in Tijuana, Mexico

<p>Abstract</p> <p>Background</p> <p>Sterile syringe access is a critical component of HIV prevention programs. Although retail pharmacies provide convenient outlets for syringe access, injection drug users (IDUs) may encounter barriers to syringe purchase even where purchase without a prescription is legal. We sought to obtain an objective measure of syringe access in Tijuana, Mexico, where IDUs report being denied or overcharged for syringes at pharmacies.</p> <p>Methods</p> <p>Trained "mystery shoppers" attempted to buy a 1 cc insulin syringe according to a predetermined script at all retail pharmacies in three Tijuana neighborhoods. The same pharmacies were surveyed by telephone regarding their syringe sales policies. Data on purchase attempts were analyzed using basic statistics to obtain an objective measure of syringe access and compared with data on stated sales policies to ascertain consistency.</p> <p>Results</p> <p>Only 46 (28.4%) of 162 syringe purchase attempts were successful. Leading reasons for unsuccessful attempts were being told that the pharmacy didn't sell syringes (35.3%), there were no syringes in stock (31.0%), or a prescription was required (20.7%). Of 136 pharmacies also surveyed by telephone, a majority (88.2%) reported selling syringes but only one-third (32.5%) had a successful mystery shopper purchase; the majority of unsuccessful purchases were attributed to being told the pharmacy didn't sell syringes. There was similar discordance regarding prescription policies: 74 pharmacies said in the telephone survey that they did not require a prescription for syringes, yet 10 of these pharmacies asked the mystery shopper for a prescription.</p> <p>Conclusions</p> <p>IDUs in Tijuana have limited access to syringes through retail pharmacies and policies and practices regarding syringe sales are inconsistent. Reasons for these restrictive and inconsistent practices must be identified and addressed to expand syringe access, reduce syringe sharing and prevent HIV transmission.</p

Expanding the Repertoire of Carbapenem-Hydrolyzing Metallo-ß-Lactamases by Functional Metagenomic Analysis of Soil Microbiota

Carbapenemases are bacterial enzymes that hydrolyze carbapenems, a group of last-resort β-lactam antibiotics used for treatment of severe bacterial infections. They belong to three β-lactamase classes based amino acid sequence (A, B, and D). The aim of this study was to elucidate occurrence, diversity and functionality of carbapenemase-encoding genes in soil microbiota by functional metagenomics. Ten plasmid libraries were generated by cloning metagenomic DNA from agricultural (n = 6) and grassland (n = 4) soil into Escherichia coli. The libraries were cultured on amoxicillin-containing agar and up to 100 colonies per library were screened for carbapenemase production by CarbaNP test. Presumptive carbapenemases were characterized with regard to DNA sequence, minimum inhibitory concentration (MIC) of β-lactams, and imipenem hydrolysis. Nine distinct class B carbapenemases, also known as metallo-beta-lactamases (MBLs), were identified in six soil samples, including two subclass B1 (GRD23-1 and SPN79-1) and seven subclass B3 (CRD3-1, PEDO-1, GRD33-1, ESP-2, ALG6-1, ALG11-1, and DHT2-1). Except PEDO-1 and ESP-2, these enzymes were distantly related to any previously described MBLs (33 to 59% identity). RAIphy analysis indicated that six enzymes (CRD3-1, GRD23-1, DHT2-1, SPN79-1, ALG6-1, and ALG11-1) originated from Proteobacteria, two (PEDO-1 and ESP-2) from Bacteroidetes and one (GRD33-1) from Gemmatimonadetes. All MBLs detected in soil microbiota were functional when expressed in E. coli, resulting in detectable imipenem-hydrolyzing activity and significantly increased MICs of clinically relevant β-lactams. Interestingly, the MBLs yielded by functional metagenomics generally differed from those detected in the same soil samples by antibiotic selective culture, showing that the two approaches targeted different subpopulations in soil microbiota. © 2016 Gudeta, Bortolaia, Pollini, Docquier, Rossolini, Amos, Wellington and Guardabassi.Grant HEALTH-F3-2011-282004(EvoTAR

Aging and memory phenomena in magnetic and transport properties of vortex matter: a brief review

There is mounting experimental evidence that strong off-equilibrium phenomena, such as ``memory'' or ``aging'' effects, play a crucial role in the physics of vortices in type II superconductors. We give a short review, based on a recently introduced schematic vortex model, of current progresses in understanding out of equilibrium vortex behaviours. We develop a unified description of ``memory'' phenomena in magnetic and transport properties, such as magnetisation loops and their ``anomalous'' 2nd peak, logarithmic creep, ``anomalous'' finite creep rate in the limit of vanishing temperature, ``memory'' and ``irreversibility'' in I-V characteristics, time dependent critical currents, ``rejuvenation'' and ``aging'' of the system response.Comment: updated versio

C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation

Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of repeat-containing C9orf72 RNA results in the production of neurotoxic dipeptide-repeat proteins (DPRs). Here, we developed a high-throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP-elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA-catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient-derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD