Respiratory syncytial virus infection in elderly adults.

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and young children. Reinfections are common throughout adult life with more severe presentations occurring in immunocompromised individuals, subjects with underlying high-risk cardiopulmonary diseases, and in the elderly. There is now a significant body of literature indicating that the impact of RSV in elderly adults is similar to that of non-pandemic influenza, both in the community and in nursing homes. Clinical manifestations of RSV infections are similar to those caused by other viral respiratory pathogens, including influenza viruses. Molecular tests (reverse transcription-PCR) now provide a rapid diagnosis. The sputum sample combined with nasopharyngeal swab increases the diagnostic yield. At the present time, treatment is mainly symptomatic. The prevention of RSV consists in various infection control strategies, such as standard precautions, especially hand washing and droplet precautions to limit the nosocomial spread. Vaccines and antiviral agents for the prevention and treatment of RSV infections in elderly adults are currently not available, but they are being developed.

Crowdsourced validation of a machine-learning classification system for autism and ADHD.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) together affect >10% of the children in the United States, but considerable behavioral overlaps between the two disorders can often complicate differential diagnosis. Currently, there is no screening test designed to differentiate between the two disorders, and with waiting times from initial suspicion to diagnosis upwards of a year, methods to quickly and accurately assess risk for these and other developmental disorders are desperately needed. In a previous study, we found that four machine-learning algorithms were able to accurately (area under the curve (AUC)>0.96) distinguish ASD from ADHD using only a small subset of items from the Social Responsiveness Scale (SRS). Here, we expand upon our prior work by including a novel crowdsourced data set of responses to our predefined top 15 SRS-derived questions from parents of children with ASD (n=248) or ADHD (n=174) to improve our model's capability to generalize to new, 'real-world' data. By mixing these novel survey data with our initial archival sample (n=3417) and performing repeated cross-validation with subsampling, we created a classification algorithm that performs with AUC=0.89±0.01 using only 15 questions.

Use of machine learning for behavioral distinction of autism and ADHD.

Although autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) continue to rise in prevalence, together affecting >10% of today's pediatric population, the methods of diagnosis remain subjective, cumbersome and time intensive. With gaps upward of a year between initial suspicion and diagnosis, valuable time where treatments and behavioral interventions could be applied is lost as these disorders remain undetected. Methods to quickly and accurately assess risk for these, and other, developmental disorders are necessary to streamline the process of diagnosis and provide families access to much-needed therapies sooner. Using forward feature selection, as well as undersampling and 10-fold cross-validation, we trained and tested six machine learning models on complete 65-item Social Responsiveness Scale score sheets from 2925 individuals with either ASD (n=2775) or ADHD (n=150). We found that five of the 65 behaviors measured by this screening tool were sufficient to distinguish ASD from ADHD with high accuracy (area under the curve=0.965). These results support the hypotheses that (1) machine learning can be used to discern between autism and ADHD with high accuracy and (2) this distinction can be made using a small number of commonly measured behaviors. Our findings show promise for use as an electronically administered, caregiver-directed resource for preliminary risk evaluation and/or pre-clinical screening and triage that could help to speed the diagnosis of these disorders.

Antibiotic prescription evaluation in the rehabilitation ward of a geriatric hospital.

OBJECTIVES: We aimed to identify the indications for antibiotic prescriptions made to patients hospitalized in the rehabilitation ward of a geriatric hospital. Our final objective was to assess those prescriptions. PATIENTS AND METHODS: Medical experts performed a prospective study of all antibiotic treatments prescribed in the rehabilitation ward over a 4-month period based on Gyssens' algorithm and on the local guidelines for anti-infective drugs. Treatments were considered appropriate when the indication, choice of agent, duration, and dose were approved by the experts. They were however considered unnecessary when the indication was incorrect, and they were deemed inappropriate when the experts approved the indication but considered that treatment modalities were not optimal. We also reviewed the prescription re-evaluation made 48 to 72hours after treatment initiation. RESULTS: We reviewed 142 prescriptions. Treatments had mainly been prescribed for respiratory tract infections (81 infections), urinary tract infections (41), skin infections (15), or abdominal infections (8). A total of 27 prescriptions (19%) were considered unnecessary mainly because a urinary tract infection diagnosis had been wrongly made (21 prescriptions). Half of the prescriptions were considered inappropriate: 38 prescriptions had an inappropriate spectrum of activity and 32 had an inadequate treatment duration. A total of 67 prescriptions (47.2%) had been reassessed 48-72hours after treatment initiation. Overall, 25 prescriptions (17.6%) were considered appropriate and were reassessed 48-72hours after treatment initiation. CONCLUSIONS: We now have a better understanding of antibiotic prescription in a rehabilitation ward context. We identified several points that need to be improved: update and improvement of the local guidelines, better training for prescribers, and creation of a supporting document for the reassessment of the prescriptions 48-72hours after treatment initiation.

Transient decrease in nociceptor GRK2 expression produces long-term enhancement in inflammatory pain.

In heterozygous mice, attenuation of G-protein-coupled receptor kinase 2 (GRK2) level in nociceptors is associated with enhanced and prolonged inflammatory hyperalgesia. To further elucidate the role of GRK2 in nociceptor function we reversibly decreased GRK2 expression using intrathecal antisense oligodeoxynucleotide (AS-ODN). GRK2 AS-ODN administration led to an enhanced and prolonged hyperalgesia induced by prostaglandin E(2), epinephrine and carrageenan. Moreover, this effect persisted unattenuated 2weeks after the last dose of antisense, well after GRK2 protein recovered, suggesting that transient attenuation of GRK2 produced neuroplastic changes in nociceptor function. Unlike hyperalgesic priming induced by transient activation of protein kinase C epsilon (PKCε), (Aley et al., 2000; Parada et al., 2003b), the enhanced and prolonged hyperalgesia following attenuation of GRK2 is PKCε- and cytoplasmic polyadenylation element binding protein (CPEB)-independent and is protein kinase A (PKA)- and Src tyrosine kinase (Src)-dependent. Finally, rats treated with GRK2 AS-ODN exhibited enhanced and prolonged hyperalgesia induced by direct activation of second messengers, adenyl cyclase, Epac or PKA, suggesting changes downstream of G-protein-coupled receptors. Because inflammation can produce a decrease in GRK2, such a mechanism could help explain a predilection to develop chronic pain, after resolution of acute inflammation.

[Incidence and clinical characteristics of symptomatic urinary infections in a geriatric hospital]. / Incidence et caractéristiques cliniques des infections urinaires symptomatiques dans un hôpital gériatrique.

UNLABELLED: OBJECTIVES AND SETTINGS: The authors had for aim to study the incidence of symptomatic urinary infections (SUTI) in elderly patients, to describe their clinical and microbiologic characteristics and first-line treatment in a geriatric hospital with 902 beds: 124 in acute care (ACF), 293 in rehabilitation and intermediate-care (RICF), and 485 in long-term-care-facilities (LTCF). METHOD: During two months in 2003, all positive urine cultures detected by the laboratory were sent to the clinician with a questionnaire on clinical signs, diagnosis of SUTI and antibiotic treatment. RESULTS: SUTI was diagnosed in 85 out of 204 positive urine cultures (40%). The incidence of SUTI was 1.86 per 1,000 patient-days (with rates of 2.63, 2.49, 1.41 per 1,000 patients-days for the ACF, RICF, LTCF respectively). For 51 cases (60%) there were only general symptoms, for 24 cases (28.2%) there were only urinary symptoms, and for 10 cases (11.8%) there were both. Escherichia coli and Proteus mirabilis were the main bacterial species involved in 57 and 14% respectively. E. coli strains were 59% resistant to amoxicillin, 55% resistant to amoxicillin-clavulanic acid, and 39% resistant to fluoroquinolones. The main antibiotics were fluoroquinolones, ceftriaxone, and amoxicillin-clavulanate, prescribed respectively in 52.5, 19, and 9% of the cases. CONCLUSION: SUTI was diagnosed in only in 40% of positive urine cultures from elderly patients hospitalized in our hospital. To improve the management of SUTI in this population, we changed our recommendations for diagnosis and treatment.

Mapping the functional anatomy of BgK on Kv1.1, Kv1.2, and Kv1.3. Clues to design analogs with enhanced selectivity.

BgK is a peptide from the sea anemone Bunodosoma granulifera, which blocks Kv1.1, Kv1.2, and Kv1.3 potassium channels. Using 25 analogs substituted at a single position by an alanine residue, we performed the complete mapping of the BgK binding sites for the three Kv1 channels. These binding sites included three common residues (Ser-23, Lys-25, and Tyr-26) and a variable set of additional residues depending on the particular channel. Shortening the side chain of Lys-25 by taking out the four methylene groups dramatically decreased the BgK affinity to all Kv1 channels tested. However, the analog K25Orn displayed increased potency on Kv1.2, which makes this peptide a selective blocker for Kv1.2 (K(D) 50- and 300-fold lower than for Kv1.1 and Kv1.3, respectively). BgK analogs with enhanced selectivity could also be made by substituting residues that are differentially involved in the binding to some of the three Kv1 channels. For example, the analog F6A was found to be >500-fold more potent for Kv1.1 than for Kv1.2 and Kv1.3. These results provide new information about the mechanisms by which a channel blocker distinguishes individual channels among closely related isoforms and give clues for designing analogs with enhanced selectivity.

Specific distribution of sodium channels in axons of rat embryo spinal motoneurones.

1. The distribution of Na+ channels and development of excitability were investigated in vitro in purified spinal motoneurones obtained from rat embryos at E14, using electrophysiological, immunocytochemical and autoradiographical methods. 2. One hour after plating the motoneurones (DIV0), only somas were present. They expressed a robust delayed rectifier K+ current (IDR) and a fast-inactivating A-type K+ current (IA). The rapid neuritic outgrowth was paralleled by the emergence of a fast-activating TTX-sensitive sodium current (INa), and by an increase in both K+ currents. 3. The change in the three currents was measured daily, up to DIV8. The large increase in INa observed after DIV2 was accompanied by the onset of excitability. Spontaneous activity was observed as from DIV6. 4. The occurrence of axonal differentiation was confirmed by the fact that (i) only one neurite per motoneurone generated antidromic action potentials; and (ii) 125I-alpha-scorpion toxin binding, a specific marker of Na+ channels, labelled only one neurite and the greatest density was observed in the initial segment. Na+ channels therefore selectively targeted the axon and were absent from the dendrites and somas. 5. The specific distribution of Na+ channels was detectable as soon as the neurites began to grow. When the neuritic outgrowth was blocked by nocodazole, no INa developed. 6. It was concluded that, in spinal embryonic motoneurone in cell culture, Na+ channels, the expression of which starts with neuritic differentiation, are selectively addressed to the axonal process, whereas K+ channels are present in the soma prior to the neuritic outgrowth.

Electromolecular propulsion (EMP): a rapid, simple method for analyzing dyes used in microscopy.

The electrokinetic molecular effect known as electromolecular propulsion (EMP) was used to examine a variety of commonly used dyes that are used as biological stains. The dyes were electrokinetically mobilized using several organic solvent mixtures on a variety of thin layer substrates. Analysis was completed in seconds to minutes. Nearly all dyes tested separated into multiple colored components. The solvents and substrates used were well suited for qualitatively analyzing a broad variety of hydrophilic and lipophilic colorants. Speed, resolving power and operational simplicity of this technique make it convenient for effectively "fingerprinting" for consistency in dye products. EMP may be broadly applied to study quality control of dyes and their stains. Components not ordinarily known to be present can be readily detected using this technology. EMP can complement or offer a versatile alternative to existing analytical methods.

Chromosomal mapping of human adenylyl cyclase genes type III, type V and type VI.

Adenylyl cyclase activity plays a central role in the regulation of most cellular processes. At least eight different adenylyl cyclases have been identified, which are endowed with various and sometimes opposing regulatory properties. Recently we have localized the human genes encoding two of these adenylyl cyclases: the gene for type II adenylyl cyclase is located on chromosome 2 (sub-band 2p15.3), the gene for type VIII is located on chromosome 8 (sub-band 8q24.2). More recently the type I gene has been located on chromosome 7 (sub-band 7p12-7p13). Using in situ hybridization, we have now localized the genes for three other adenylyl cyclases: the type III gene has been localized on chromosome 2 in the sub-band 2p22-2p24, the type V gene on chromosome 3 at position 3q13.2-3q21, and the type VI gene on chromosome 12 at position 12q12-12q13. It therefore appears that all adenylyl cyclase genes, known at present are located on different chromosomes and thus are likely to be independently regulated.

Chemoelectronic mobilization of chemical species in low-conductivity fluids: new electrokinetic effect.

An electrokinetic phenomenon is reported here which differs from its classical counterparts most distinctively by nonlinear conductivity and mobility. Neither purely electrolytic nor electrostatic in nature, this phenomenon is presumed to involve subtle charge transfer effects and association reactions permitting a controlled "chemoelectric" mobilization. In its electrokinetic manifestation, this phenomenon can be used to mobilize chemical species commonly with migration rates orders of magnitude greater than can be achieved electrophoretically and is shown to induce the movement of nonpolar molecules, such as aromatic hydrocarbons, at rates exceeding several centimeters per minute in easily achievable voltage gradients. The operational technique, developed as a separations method used for demonstrating the effect, is called "electromolecular propulsion".