Isolation of a Novel Phage with Activity against Streptococcus mutans Biofilms

peer-reviewedStreptococcus mutans is one of the principal agents of caries formation mainly, because of its ability to form biofilms at the tooth surface. Bacteriophages (phages) are promising antimicrobial agents that could be used to prevent or treat caries formation by S. mutans. The aim of this study was to isolate new S. mutans phages and to characterize their antimicrobial properties. A new phage, ɸAPCM01, was isolated from a human saliva sample. Its genome was closely related to the only two other available S. mutans phage genomes, M102 and M102AD. ɸAPCM01 inhibited the growth of S. mutans strain DPC6143 within hours in broth and in artificial saliva at multiplicity of infections as low as 2.5x10-5. In the presence of phage ɸAPCM01 the metabolic activity of a S. mutans biofilm was reduced after 24 h of contact and did not increased again after 48 h, and the live cells in the biofilm decreased by at least 5 log cfu/ml. Despite its narrow host range, this newly isolated S. mutans phage exhibits promising antimicrobial properties

Patterns of concurrent substance use among adolescent nonmedical ADHD stimulant users

Objectives: There are growing concerns about nonmedical use of ADHD stimulants among adolescents; yet, little is known whether there exist heterogeneous subgroups among adolescents with nonmedical ADHD stimulant use according to their concurrent substance use. Methods: We used latent class analysis (LCA) to examine patterns of past-year problematic substance use (meeting any criteria for abuse or dependence) in a sample of 2203 adolescent participants from the National Surveys on Drug Use and Health 2006–2011 who reported past-year nonmedical use of ADHD stimulants. Multivariable latent regression was used to assess the association of socio-demographic characteristics, mental health and behavioral problems with the latent classes. Results: The model fit indices favored a four-class model, including a large class with frequent concurrent use of alcohol and marijuana (Alcohol/marijuana class; 41.2%), a second large class with infrequent use of other substances (Low substance class, 36.3%), a third class characterized by more frequent misuse of prescription drugs as well as other substances (Prescription drug + class; 14.8%), and finally a class characterized by problematic use of multiple substances (Multiple substance class; 7.7%). Compared with individuals in Low substance class, those in the other three classes were all more likely to report mental health problems, deviant behaviors and substance abuse service use. Conclusions: Adolescent nonmedical ADHD stimulants users are a heterogeneous group with distinct classes with regard to concurrent substance use, mental health and behavioral problems. The findings have implications for planning of tailored prevention and treatment programs to curb stimulant use for this age group

Correlates of nonmedical use of stimulants and methamphetamine use in a national sample

BACKGROUND: Despite chemical similarities, ADHD stimulants and methamphetamine have distinct use patterns in the community. This study compared the characteristics of nonmedical ADHD stimulants users and methamphetamine users in a household sample. METHODS: In data from the 2009-2011 National Survey on Drug Use and Health, adult and adolescent stimulant users were categorized into three mutually exclusive subgroups: nonmedical ADHD stimulant users only (STM users), methamphetamine users (METH users), and both nonmedical ADHD stimulant and methamphetamine users (STM/METH users). Multivariate logistic regression analyses identified the substance comorbidity, mental health, and deviant behavior characteristics associated with these three groups. RESULTS: Compared to adolescent STM users, STM/METH users were more likely to be female, younger and uninsured while METH users were more likely to be younger, in a minority group and from a higher-income family. Compared to adult STM users, METH and STM/METH users were more likely to be male, older, uninsured, no longer married, and to be from rural areas. Adolescent METH users were more likely than STM users to report illegal drug use while adult METH users were less likely to report prescription drug use than their STM user counterparts. Overall, adult and adolescent STM/METH users were more likely to report substance use, mental health problems and deviant behaviors compared to STM users. CONCLUSION: The characteristics of STM users differ from METH and STM/METH users, and their associations with substance use and psychiatric comorbidities differ by age. Findings have implications for understanding the risks for stimulant use in different age subgroups

Patterns of concurrent substance use among nonmedical ADHD stimulant users: Results from the National Survey on Drug Use and Health

Aims: To examine patterns of concurrent substance use among adults with nonmedical ADHD stimulant use. Methods: We used latent class analysis (LCA) to examine patterns of past-year problematic substance use (meeting any criteria for abuse or dependence) in a sample of 6103 adult participants from the National Surveys on Drug Use and Health 2006–2011 who reported past-year nonmedical use of ADHD stimulants. Multivariable latent regression was used to assess the association of socio-demographic characteristics, mental health and behavioral problems with the latent classes. Results: A four-class model had the best model fit, including (1) participants with low probabilities for any problematic substance use (Low substance class, 53.3%); (2) problematic users of all types of prescription drugs (Prescription drug class, 13.3%); (3) participants with high probabilities of problematic alcohol and marijuana use (Alcohol–marijuana class, 28.8%); and (4) those with high probabilities of problematic use of multiple drugs and alcohol (Multiple substance class, 4.6%). Participants in the 4 classes had distinct socio-demographic, mental health and service use profiles with those in the Multiple substance class being more likely to report mental health and behavioral problems and service use. Conclusion: Nonmedical users of ADHD stimulants are a heterogeneous group with a large subgroup with low prevalence of problematic use of other substances. These subgroups have distinct patterns of mental health comorbidity, behavior problems and service use, with implications for prevention and treatment of nonmedical stimulant use

Brazilian guideline for the treatment of patients with opioids dependence syndrome

There is a relatively low prevalence of opioid use in Brazil, particularly involving the non-medical use of codeine and opiate-containing syrups. However, opioid dependence syndrome shows a significant total impact on mortality and morbidity. Over the past 20 years, scientific progress has changed our understanding of the nature of opioid addiction and its various possible treatments. Addiction is a chronic illness treatable if the treatment is well-delivered and tailored to the needs of the particular patient. There is indeed an array of treatments that can effectively reduce drug use, help manage drug cravings, prevent relapses and restore people to productive social functioning. The treatment of drug addiction will be part of long-term, medical, psychological, and social perspectives. This guideline aims at providing guidance to psychiatrists and other mental health professionals who care for patients with Opioid Dependence Syndrome. It comments on the somatic and psychosocial treatment that is used for such patients, and reviews scientific evidences and their strength. Also, the essential historical, epidemiological and neurobiological aspects of Opioid Dependence are reviewed.Existe uma prevalência relativamente baixa do uso de ópioides no Brasil, em particular envolvendo o uso não médico da codeína e de xaropes que contêm opióides. No entanto, a síndrome de dependência apresenta um significativo impacto total na mortalidade e morbidade. Nos últimos 20 anos, o avanço científico tem modificado nosso entendimento sobre a natureza da adição aos opióides e os variados tratamentos possíveis. A adição é uma doença crônica tratável se o tratamento for realizado e adaptado tendo em vista as necessidades do paciente específico. Há, de um fato, um conjunto de tratamentos que podem efetivamente reduzir o uso da droga, ajudar a gerenciar a fissura pela droga, prevenir recaídas e recuperar as pessoas para o funcionamento social produtivo. O tratamento da dependência de drogas será parte de perspectivas de longo prazo do ponto de vista médico, psicológico e social. Esta diretriz almeja fornecer um guia para os psiquiatras e outros profissionais de saúde que tratam de pacientes com Síndrome de Dependência de Opióides. Ela tece comentários sobre o tratamento somático e psicossocial que é utilizado nesses pacientes e revisa as evidências científicas e seu poder. Da mesma forma, os aspectos históricos, epidemiológicos e neurobiológicos da dependência de opióides são revisados.Universidade de São Paulo Hospital de Clínicas Instituto de PsiquiatriaFaculdade de Medicina do ABCJohns Hopkins University School of MedicineAssociação Brasileira de Psiquiatria Departamento de Dependência QuímicaHospital Albert EinsteinUniversidade Federal de São Paulo (UNIFESP)UNIADUNIFESPSciEL

A Long Spell of Uncertainity

We find ourselves in a period of sustained economic uncertainty. Today, like 6 months ago, the U.S. economy is on the brink of a recession. Weakness in lending activity, coupled with weakness in the housing sector and related manufacturing industries has stymied economic growth since late 2007. At times, recession seems imminent. But, the official measures, such as quarterly gross domestic product, do not clearly signal that the economy is contracting. Further, prices are rising rapidly for food and energy. That is the uncertainty. Will 2008 be remembered as a recession year, or as a period of disappointing but slow growth? And, will 2008 be known as the year when inflation reignited in America. In some sense, the answer does not matter. The United States and its citizens already are experiencing some of the consequences of recession, and of higher inflation. Job counts are declining and unemployment is rising. Many face the prospect of losing their homes. Prices including food and energy are rising 2% faster than in most recent years. But, of course, the answer matters quite a lot. If the U.S. economy falls into recession, or if a recession has already begun, job losses will accelerate and unemployment will rise sharply. The real estate and financial markets may spiral down faster. There is also a risk that prices increases will accelerate if inflation in food and energy spreads into wage inflation impacting a broad spectrum of sectors. Our view is that the economy will avoid both a significant recession and rapid inflation. Strong exports will encourage growth, and consumers and the financial sector will slowly work their way through their current difficulties. Inflation largely will be contained to the food and energy sectors. But, the scenario is far from rosy. We expect weak economic growth through 2008 and early 2009, and elevated inflation rates through 2010. In particular, we expected annual growth in real GDP of 1.1% in 2008, 1.7% in 2009. GDP growth rates only returns to trend growth of 2.8% in 2010. Inflation will hit 4.0% in 2008, and will be well above 2% in subsequent years, at 2.6% in 2009, and 2.7% in 2010. A significant slowdown will be avoided because the weak dollar will encourage strong exports, and because consumer spending will expand modestly despite a weak employment situation and high energy prices. Consumer confidence has declined rapidly but consumer spending should stay steady thanks to lower interest rates, and in the very short-term, federal government rebate checks. Current high energy prices also are expected to stabilize, and therefore, will not cause even further strain on consumer spending for other goods and services. This relatively positive scenario naturally assumes that the U.S. economy will avoid other major dislocations. The economy may fall into a significant recession if there are other major disruptions in the financial system that limit access to capital. Inflation may spike further if oil prices rise or additional weather causes further increases in food prices

High resolution clustering of Salmonella enterica serovar Montevideo strains using a next-generation sequencing approach

<p>Abstract</p> <p>Background</p> <p>Next-Generation Sequencing (NGS) is increasingly being used as a molecular epidemiologic tool for discerning ancestry and traceback of the most complicated, difficult to resolve bacterial pathogens. Making a linkage between possible food sources and clinical isolates requires distinguishing the suspected pathogen from an environmental background and placing the variation observed into the wider context of variation occurring within a serovar and among other closely related foodborne pathogens. Equally important is the need to validate these high resolution molecular tools for use in molecular epidemiologic traceback. Such efforts include the examination of strain cluster stability as well as the cumulative genetic effects of sub-culturing on these clusters. Numerous isolates of <it>S</it>. Montevideo were shot-gun sequenced including diverse lineage representatives as well as numerous replicate clones to determine how much variability is due to bias, sequencing error, and or the culturing of isolates. All new draft genomes were compared to 34 <it>S</it>. Montevideo isolates previously published during an NGS-based molecular epidemiological case study.</p> <p>Results</p> <p>Intraserovar lineages of <it>S</it>. Montevideo differ by thousands of SNPs, that are only slightly less than the number of SNPs observed between <it>S</it>. Montevideo and other distinct serovars. Much less variability was discovered within an individual <it>S</it>. Montevideo clade implicated in a recent foodborne outbreak as well as among individual NGS replicates. These findings were similar to previous reports documenting homopolymeric and deletion error rates with the Roche 454 GS Titanium technology. In no case, however, did variability associated with sequencing methods or sample preparations create inconsistencies with our current phylogenetic results or the subsequent molecular epidemiological evidence gleaned from these data.</p> <p>Conclusions</p> <p>Implementation of a validated pipeline for NGS data acquisition and analysis provides highly reproducible results that are stable and predictable for molecular epidemiological applications. When draft genomes are collected at 15×-20× coverage and passed through a quality filter as part of a data analysis pipeline, including sub-passaged replicates defined by a few SNPs, they can be accurately placed in a phylogenetic context. This reproducibility applies to all levels within and between serovars of <it>Salmonella </it>suggesting that investigators using these methods can have confidence in their conclusions.</p

A Long Spell of Uncertainty

We find ourselves in a period of sustained economic uncertainty. Today, like 6 months ago, the U.S. economy is on the brink of a recession. Weakness in lending activity, coupled with weakness in the housing sector and related manufacturing industries has stymied economic growth since late 2007. At times, recession seems imminent. But, the official measures, such as quarterly gross domestic product, do not clearly signal that the economy is contracting. Further, prices are rising rapidly for food and energy. That is the uncertainty. Will 2008 be remembered as a recession year, or as a period of disappointing but slow growth? And, will 2008 be known as the year when inflation reignited in America. I

Effect of Treatment, during Primary Infection, on Establishment and Clearance of Cellular Reservoirs of HIV-1

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatmen

Operational definition of precipitated opioid withdrawal

Background Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal.MethodsPeople (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA).ResultsWithin 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1–40, 41–80, and 81–100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal.ConclusionData suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal