Efficacy of an intensive outpatient rehabilitation program in alcoholism: Predictors of outcome 6 months after treatment

Treatment of alcohol-dependent patients was primarily focused on inpatient settings in the past decades. The efficacy of these treatment programs has been evaluated in several studies and proven to be sufficient. However, with regard to the increasing costs in public healthcare systems, questions about alternative treatment strategies have been raised. Meanwhile, there is growing evidence that outpatient treatment might be comparably effective as inpatient treatment, at least for subgroups of alcohol dependents. On that background, the present study aimed to evaluate the efficacy of a high-structured outpatient treatment program in 103 alcohol-dependent patients. 74 patients (72%) terminated the outpatient treatment regularly. At 6 months' follow-up, 95% patients were successfully located and personally re-interviewed. Analyses revealed that 65 patients (64%) were abstinent at the 6-month follow-up evaluation and 37 patients ( 36%) were judged to be non-abstinent. Pretreatment variables which were found to have a negative impact (non-abstinence) on the 6-month outcome after treatment were a higher severity of alcohol dependence measured by a longer duration of alcohol dependence, a higher number of prior treatments and a stronger alcohol craving (measured by the Obsessive Compulsive Drinking Scale). Further patients with a higher degree of psychopathology measured by the Beck Depression Inventory (depression) and State-Trait Anxiety Inventory (anxiety) relapsed more often. In summary, results of this study indicate a favorable outcome of socially stable alcohol-dependent patients and patients with a lower degree of depression, anxiety and craving in an intensive outpatient rehabilitation program

Allergic bronchopulmonary aspergillosis with coexistant aspergilloma: a case report

<p>Abstract</p> <p>Introduction</p> <p>The coexistence of allergic bronchopulmonary aspergillosis and aspergilloma is rare.</p> <p>Case presentation</p> <p>We present the case of a 56-year-old Caucasian man who worked as a farmer, with infiltrates in the right lower and middle lung lobes, partial consolidation of the middle lobe and with previous diagnosis of chronic obstructive bronchitis. Evaluation of our patient led to the diagnosis of allergic bronchopulmonary aspergillosis with coexistent aspergilloma in the right lower lobe. He was treated with oral methylprednisolone and itraconazole. At the five-year follow-up he is without any sign of recurrence.</p> <p>Conclusion</p> <p>Aspergillus infection after the inhalation of spores in the form of a hypersensitivity reaction and saprophytic colonization can be coexistent.</p

Effect of closed endotracheal suction in high-frequency ventilated premature infants measured with electrical impedance tomography

Objective: To determine the global and regional changes in lung volume during and after closed endotracheal tube (ETT) suction in high-frequency ventilated preterm infants with respiratory distress syndrome (RDS). Design: Prospective observational clinical study. Setting: Neonatal intensive care unit. Patients: Eleven non-muscle relaxed preterm infants with RDS ventilated with open lung high-frequency ventilation (HFV). Interventions: Closed ETT suction. Measurements and results: Changes in global and regional lung volume were measured with electrical impedance tomography. ETT suction resulted in an acute loss of lung volume followed by spontaneous recovery with a median residual loss of 3.3% of the maximum volume loss. The median stabilization time was 8 s. At the regional level, the lung volume changes during and after ETT suction were heterogeneous in nature. Conclusions: Closed ETT suction causes an acute, transient and heterogeneous loss of lung volume in premature infants with RDS treated with open lung HFV

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination

BACKGROUND: In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. METHODS: We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. RESULTS: With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. CONCLUSIONS: Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts

Cosmological flux noise and measured noise power spectra in SQUIDs

The understanding of the origin of $1/f$ magnetic flux noise commonly observed in superconducting devices such as SQUIDS and qubits is still a major unsolved puzzle. Here we discuss the possibility that a significant part of the observed low-frequency flux noise measured in these devices is ultimately seeded by cosmological fluctuations. We consider a theory where a primordial flux noise field left over in unchanged form from an early inflationary or quantum gravity epoch of the universe intrinsically influences the phase difference in SQUIDs and qubits. The perturbation seeds generated by this field can explain in a quantitatively correct way the form and amplitude of measured low-frequency flux noise spectra in SQUID devices if one takes as a source of fluctuations the primordial power spectrum of curvature fluctuations as measured by the Planck collaboration. Our model predicts flux noise with a spectrum given by an $1/f^{2-n_s}$ spectrum, where $n_s=0.96$ is the spectral index of the near-scale invariant primordial density fluctuations. For the typical amplitude of this cosmologically generated universal flux noise we theoretically calculate the average value $\delta \Phi /\Phi_0 =3.41 \cdot 10^{-6}$ at 1Hz. These theoretical predictions are in excellent agreement with recent low-frequency flux noise measurements of various experimental groups. Magnetic flux noise, so far mainly considered as a nuisance for electronic devices, may thus contain valuable information about fluctuation spectra in the very early universe.Comment: 7 pages, 3 figures. Newly written updated version. Final version as accepted by Scientific Report

First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy

Objectives: Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo. Methods: HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint. Results: All 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1 BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration. Conclusions: Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538). © 2011 Anton et al

Rational Design of a Plasmid Origin That Replicates Efficiently in Both Gram-Positive and Gram-Negative Bacteria

Background: Most plasmids replicate only within a particular genus or family

Effectiveness of motivational interviewing and physical activity on prescription on leisure exercise time in subjects suffering from mild to moderate hypertension

<p>Abstract</p> <p>Background</p> <p>Physical inactivity is considered to be the strongest individual risk factor for poor health in Sweden. It has been shown that increased physical activity can reduce hypertension and the risk of developing cardiovascular diseases. The objective of the present pilot study was to investigate whether a combination of Motivational Interviewing (MI) and Physical Activity on Prescription (PAP) would increase leisure exercise time and subsequently improve health-related variables.</p> <p>Methods</p> <p>This pilot study was of a repeated measures design, with a 15 months intervention in 31 patients with mild to moderate hypertension. Primary outcome parameter was leisure exercise time and secondary outcome parameters were changes in blood pressure, Body Mass Index (BMI), waist circumference, lipid status, glycosylated haemoglobin (HbA1c) and maximal oxygen uptake (VO_{2 max}). Assessments of the outcome parameters were made at baseline and after 3, 9 and 15 months.</p> <p>Results</p> <p>Leisure exercise time improved significantly from < 60 min/week at baseline to a mean activity level of 300 (± 165) minutes/week at 15 months follow up. Furthermore, statistically significant improvements (p < 0.05) were observed in systolic (-14,5 ± 8.3 mmHg) and diastolic blood pressure (-5,1 ± 5.8 mmHg), heart rate (-4.9 ± 8.7 beats/min, weight (-1.2 ± 3.4 kg) BMI -0.6 ± 1.2 kg/m²), waist circumference (-3.5 ± 4.1 cm) as well as in VO_{2 max}(2.94 ± 3.8 ml/kg and 0.23, ± 0.34 lit/min) upon intervention as compared to baseline.</p> <p>Conclusions</p> <p>A 15 month intervention period with MI, in combination with PAP, significantly increased leisure exercise time and improved health-related variables in hypertensive patients. This outcome warrants further research to investigate the efficacy of MI and PAP in the treatment of mild to moderate hypertension.</p

A Synaptic Mechanism for Temporal Filtering of Visual Signals

The visual system transmits information about fast and slow changes in light intensity through separate neural pathways. We used in vivo imaging to investigate how bipolar cells transmit these signals to the inner retina. We found that the volume of the synaptic terminal is an intrinsic property that contributes to different temporal filters. Individual cells transmit through multiple terminals varying in size, but smaller terminals generate faster and larger calcium transients to trigger vesicle release with higher initial gain, followed by more profound adaptation. Smaller terminals transmitted higher stimulus frequencies more effectively. Modeling global calcium dynamics triggering vesicle release indicated that variations in the volume of presynaptic compartments contribute directly to all these differences in response dynamics. These results indicate how one neuron can transmit different temporal components in the visual signal through synaptic terminals of varying geometries with different adaptational properties

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. METHODS: We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. RESULTS: The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. CONCLUSIONS: The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways