Early events of HIV-1 infection: can signaling be the next therapeutic target?

Intracellular signaling events are signposts of biological processes, which govern the direction and action of biological activities. Through millions of years of evolution, pathogens, such as viruses, have evolved to hijack host cell machinery to infect their targets and are therefore dependent on host cell signaling for replication. This review will detail our current understanding of the signaling events that are important for the early steps of HIV-1 replication.

Adverse drug reactions causing admission to a paediatric hospital: a pilot study.

What Is Known And Objective: It is known that adverse drug reactions (ADRs) cause admission to hospital in adults and children. A recent adult study showed that ADRs are an important and frequent cause of hospital admission. The objective of this study is to develop methodology to ascertain the current burden of ADRs through a prospective analysis of all unplanned admissions to a paediatric hospital.

Labeling of multiple HIV-1 proteins with the biarsenical-tetracysteine system.

Due to its small size and versatility, the biarsenical-tetracysteine system is an attractive way to label viral proteins for live cell imaging. This study describes the genetic labeling of the human immunodeficiency virus type 1 (HIV-1) structural proteins (matrix, capsid and nucleocapsid), enzymes (protease, reverse transcriptase, RNAse H and integrase) and envelope glycoprotein 120 with a tetracysteine tag in the context of a full-length virus. We measure the impact of these modifications on the natural virus infection and, most importantly, present the first infectious HIV-1 construct containing a fluorescently-labeled nucleocapsid protein.

Using the Delphi technique to determine which outcomes to measure in clinical trials: recommendations for the future based on a systematic review of existing studies.

Ian Sinha and colleagues advise that when using the Delphi process to develop core outcome sets for clinical trials, patients and clinicians be involved, researchers and facilitators avoid imposing their views on participants, and attrition of participants be minimized.

Urinary biomarkers in hexachloro-1:3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression.

Hexachloro-1:3-butadiene (HCBD) causes kidney injury specific to the pars recta of the proximal tubule. In the present studies, injury to the nephron was characterized at 24 h following a single dose of HCBD, using a range of quantitative urinary measurements, renal histopathology and gene expression. Multiplexed renal biomarker measurements were performed using both the Meso Scale Discovery (MSD) and Rules Based Medicine platforms.

Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists.

Objectives: To provide information on the frequency and reasons for outcome reporting bias in clinical trials.

Design: Trial protocols were compared with subsequent publication(s) to identify any discrepancies in the outcomes reported, and telephone interviews were conducted with the respective trialists to investigate more extensively the reporting of the research and the issue of unreported outcomes.

Participants: Chief investigators, or lead or coauthors of trials, were identified from two sources: trials published since 2002 covered in Cochrane systematic reviews where at least one trial analysed was suspected of being at risk of outcome reporting bias (issue 4, 2006; issue 1, 2007, and issue 2, 2007 of the Cochrane library); and a random sample of trial reports indexed on PubMed between August 2007 and July 2008.

Depression in physical illness.

Depressive illnesses are common in the general population and are significantly more common in those with physical illnesses. The symptoms of depression may go unrecognised in medical patients, with consequent under-diagnosis and under-treatment. Co-morbid depression is associated with increased morbidity, poorer function, increased healthcare costs and increased mortality.

Reducing chimera formation during PCR amplification to ensure accurate genotyping.

Measurements of population diversity are fundamental to the reconstruction of the evolutionary and epidemiological history of organisms. Commonly used protocols to measure population diversity using the polymerase chain reaction (PCR) are prone to the introduction of artificial chimeras. These are often difficult to detect and can confound the correct interpretation of results due to the false generation of recombinants when the underlying DNA sample contains multiple distinct templates.

Who is referred to neurology clinics?--the diagnoses made in 3781 new patients.

Objective: Information on the nature and relative frequency of diagnoses made in referrals to neurology outpatient clinics is an important guide to priorities in services, teaching and research. Previous studies of this topic have been limited by being of only single centres or lacking in detail. We aimed to describe the neurological diagnoses made in a large series of referrals to neurology outpatient clinics.

The Malawi Developmental Assessment Tool (MDAT): the creation, validation, and reliability of a tool to assess child development in rural African settings.

Background: Although 80% of children with disabilities live in developing countries, there are few culturally appropriate developmental assessment tools available for these settings. Often tools from the West provide misleading findings in different cultural settings, where some items are unfamiliar and reference values are different from those of Western populations.

Methods And Findings: Following preliminary and qualitative studies, we produced a draft developmental assessment tool with 162 items in four domains of development.

Accurately measuring recombination between closely related HIV-1 genomes.

Retroviral recombination is thought to play an important role in the generation of immune escape and multiple drug resistance by shuffling pre-existing mutations in the viral population. Current estimates of HIV-1 recombination rates are derived from measurements within reporter gene sequences or genetically divergent HIV sequences. These measurements do not mimic the recombination occurring in vivo, between closely related genomes.

The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews.

Objective: To examine the prevalence of outcome reporting bias-the selection for publication of a subset of the original recorded outcome variables on the basis of the results-and its impact on Cochrane reviews.

Design: A nine point classification system for missing outcome data in randomised trials was developed and applied to the trials assessed in a large, unselected cohort of Cochrane systematic reviews. Researchers who conducted the trials were contacted and the reason sought for the non-reporting of data.

Feasibility study to inform the design of a randomised controlled trial to eradicate Pseudomonas aeruginosa infection in individuals with cystic fibrosis.

Background: There are controversies about the most effective treatment to eradicate first growth of Pseudomonas aeruginosa (P aeruginosa) from the lower airways of patients with cystic fibrosis (CF). UK guidelines recommend oral treatment, but some advocate intravenous (IV) treatment. The objective of this study was to assess the feasibility of conducting a randomised controlled trial comparing two treatment strategies to eradicate P aeruginosa in CF patients.

Vaccines for preventing influenza in people with cystic fibrosis.

Background: Viral respiratory tract infections in people with cystic fibrosis (CF) have a deteriorating effect on their lung function and disease progression. Annual influenza vaccination is therefore commonly recommended for people with CF.

Objectives: To assess the effectiveness of influenza vaccination for people with CF.

Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride-induced hepatic injury in the Hanover Wistar rat.

Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD-1) is increased in the urine of rats with carbon tetrachloride (CCl(4))-induced hepatotoxicity. The present experiments aimed to investigate further the usefulness of urinary SOD-1 as a non-invasive biomarker of liver injury. Two investigations were carried out, a dose response study and a time course study.

Women's experiences of participating in the Magpie Trial: a postal survey in the United Kingdom.

Background: The Magpie Trial compared magnesium sulfate with placebo for women with preeclampsia. The objective of this study was to explore women's views and experiences of participating in the Magpie Trial in the United Kingdom.

Methods: Postal questionnaires were sent to 771 women participants in the Magpie Trial to assess long-term health of UK women and children.

Symptoms 'unexplained by organic disease' in 1144 new neurology out-patients: how often does the diagnosis change at follow-up?

It has been previously reported that a substantial proportion of newly referred neurology out-patients have symptoms that are considered by the assessing neurologist as unexplained by 'organic disease'. There has however been much controversy about how often such patients subsequently develop a disease diagnosis that, with hindsight, would have explained the symptoms. We aimed to determine in a large sample of new neurology out-patients: (i) what proportion are assessed as having symptoms unexplained by disease and the diagnoses given to them; and (ii) how often a neurological disorder emerged which, with hindsight, explained the original symptoms.

Perspectives of normal child development in rural Malawi - a qualitative analysis to create a more culturally appropriate developmental assessment tool.

Background: Child development in developing countries is often evaluated using assessment tools created for 'Western' settings. Recent work has demonstrated that, for certain developmental milestones, 'Western' tools may be inaccurate as they include items unfamiliar to children of different cultural settings.

Methods: We used qualitative methods to gather information about normal development in an African setting.

Neurology out-patients with symptoms unexplained by disease: illness beliefs and financial benefits predict 1-year outcome.

Background: Patients whose symptoms are 'unexplained by disease' often have a poor symptomatic outcome after specialist consultation, but we know little about which patient factors predict this. We therefore aimed to determine predictors of poor subjective outcome for new neurology out-patients with symptoms unexplained by disease 1 year after the initial consultation.

Method: The Scottish Neurological Symptom Study was a 1-year prospective cohort study of patients referred to secondary care National Health Service neurology clinics in Scotland (UK).

Outcomes in clinical trials of inhaled corticosteroids for children with asthma are narrowly focussed on short term disease activity.

Background: Little work has been done to determine which outcomes should be measured in randomised controlled trials (RCTs) in children with asthma. Drug regulatory authorities require that short term disease activity is measured, but other outcome domains are not mandatory for licensing and marketing purposes. We aimed to identify whether any domains were underrepresented in RCTs of regular therapies for children with asthma over a 20 year period, and to examine what consistency there was between RCTs in the outcomes used to assess the domains.

Neutrophil TLR4 expression is reduced in the airways of infants with severe bronchiolitis.

Background: In respiratory syncytial virus (RSV) bronchiolitis, neutrophils account for >80% of cells recovered from the airways in bronchoalveolar lavage (BAL) fluid. This study investigated neutrophil activation and Toll-like receptor (TLR) expression in the blood and lungs of infants with severe RSV bronchiolitis.

Methods: BAL fluid and (blood) samples were collected from 24 (16) preterm and 23 (15) term infants ventilated with RSV bronchiolitis, and 12 (8) control infants.