A universal fluid cell for the imaging of biological specimens in the atomic force microscope.

Recently, atomic force microscope (AFM) manufacturers have begun producing instruments specifically designed to image biological specimens. In most instances, they are integrated with an inverted optical microscope, which permits concurrent optical and AFM imaging. An important component of the set-up is the imaging chamber, whose design determines the nature of the experiments that can be conducted. Many different imaging chamber designs are available, usually designed to optimize a single parameter, such as the dimensions of the substrate or the volume of fluid that can be used throughout the experiment. In this report, we present a universal fluid cell, which simultaneously optimizes all of the parameters that are important for the imaging of biological specimens in the AFM. This novel imaging chamber has been successfully tested using mammalian, plant, and microbial cells.

A new rating scale to evaluate the potential benefit of therapeutic drug monitoring

Aims: Therapeutic Drug Monitoring (TDM) is an established tool to optimize thepharmacotherapy with immunosupressants, antibiotics, antiretroviral agents, anticonvulsantsand psychotropic drugs. The TDM expert group of the Association ofNeuropsychopharmacolgy and Pharmacopsychiatry recommended clinical guidelinesfor TDM of psychotropic drugs in 2004 and in 2011. They allocate 4 levelsof recommendation based on studies reporting plasma concentrations and clinicaloutcomes. To evaluate the additional benefit for drugs without direct evidence forTDM and to verify the recommendation levels of the expert group the authorsbuilt a new rating scale. Methods: This rating scale included 28 items and wasdivided in 5 categories: Efficacy, toxicity, pharmacokinetics, patient characteristicsand cost effectiveness. A literature search was performed for 10 antidepressants,10 antipsychotics, 8 drugs used in the treatment of substance related disordersand lithium, thereafter, a comparison with the assessment of the TDMexpert group was carried out. Results: The antidepressants as well as the antipsychoticsshowed a high and significant correlation with the recommendations inthe consensus guidelines. However, meanderings could be detected for the drugsused in the therapy of substance related disorders, for which TDM is mostly notestablished yet. The result of the antidepressants and antipsychotics permits aclassification of the reachable points; upper 13 - TDM strongly recommended10 to 13 - TDM recommended, 8 to 10 - TDM useful and below 8 - TDMpotentially useful. Conclusion: These results suggest this rating scale is sensitiveto detect the appropriateness of TDM for drug treatment. For those drugs TDM isnot established a more objective estimation is possible, thus the scoring helps tofocus on the most likely drugs to require TDM.

Accès sans prescription aux statines: bénéfique ou délétère. [Over-the-counter statins: benefit or harmful?]

Making statin available over the counter is one of the measures proposed to correct its underuse. Since May 2004, simvastatin 10 mg is sold over the counter in Great Britain. But uncertainties persist concerning the efficacy of statin in primary prevention and at a 10 mg dose. Finally, there is a risk of side effects and drug interactions. Beyond the correction of statin underuse and the hope of coronary heart disease mortality reduction, the British decision highlighted the will to give individuals a sense of responsibility concerning their health and its financial cost. Anyway, the benefit of switching statin from prescription to over the counter should be experimentally evaluated before its introduction.

Universal features of personality traits from the observer's perspective: Data from 50 cultures

To test hypotheses about the universality of personality traits, college students in 50 cultures identified an adult or college-aged man or woman whom they knew well and rated the 11,985 targets using the 3rd-person version of the Revised NEO Personality Inventory. Factor analyses within cultures showed that the normative American self-report structure was clearly replicated in most cultures and was recognizable in all. Sex differences replicated earlier self-report results, with the most pronounced differences in Western cultures. Cross-sectional age differences for 3 factors followed the pattern identified in self-reports, with moderate rates of change during college age and slower changes after age 40. With a few exceptions, these data support the hypothesis that features of personality traits are common to all human groups.

The Universal Protein Resource (UniProt) in 2010.

The primary mission of UniProt is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 3 weeks and can be accessed online for searches or download at http://www.uniprot.org.

The quality of primary care in a country with universal health care coverage

Cet article a été réalisé dans le but d'évaluer la qualité des soins fournie à une population âgée de 50 à 80 ans suivie dans 4 policliniques médicales universitaires de Suisse, à savoir Bâle, Zurich, Genève et Lausanne. Nous avons sélectionné 37 indicateurs de qualité qui ont été développés et préalablement évalués au Etats-Unis. Ces indicateurs ont été divisés en 2 sous-groupes distincts : les indicateurs de prévention et les indicateurs concernant les facteurs de risque cardiovasculaires.¦L'étude a inclus des patients âgés de 50 à 80 ans avec un suivi d'un minimum de 1 an par un médecin dans l'une des policliniques de Suisse. Nous avons limité notre étude à ce groupe d'âge, afin d'avoir une prévalence élevée de facteur de risque cardiovasculaire et plus d'indications à des tests de dépistages. Les dossiers médicaux des patients ont été sélectionnés selon un mode aléatoire en prenant 250 dossiers par centre.¦L'enjeu principal de cette étude était de déterminer le niveau de soins fournis en Suisse dans les policliniques médicales universitaires. Il a été également possible de mettre en évidence les secteurs de prévention pour lesquels le taux d'application est encore insuffisant. Nous avons par la même occasion comparé nos résultats à ceux obtenus aux Etats-Unis, sachant que ce pays a un système d'évaluation de la qualité des soins qui fournit chaque années des statistiques à ce sujet.¦Les résultats de notre étude montrent qu'en Suisse les adultes reçoivent 69% des mesures de prévention recommandées mais que ces taux diffèrent d'un indicateur à l'autre. Les indicateurs à propos de la tension artérielle et de la mesure du poids (les 2 95%) ont plus souvent été réalisés durant les consultations que les indicateurs concernant l'arrêt du tabagisme (72%), les cancers du sein (40%), du colon (35%) et la vaccination annuelle contre la grippe (35.2% chez les patients de >65 ans et 29.3% chez les patient de <65 ans avec une maladie chronique). 83% des patients reçoivent les mesures préventives concernant les facteurs de risque cardiovasculaire, avec >75% pour l'hypertension, le diabète et la dyslipidémie. Cependant, l'examen des pieds est effectué chez seulement 50% des patients présentant un diabète.¦De même, nous avons pu démontrer que les femmes (65.3%) et les personnes âgées de plus de 65 ans (68.0%) reçoivent moins de mesures préventives que les hommes (72.2%) et les personnes plus jeunes (70.1%).¦Ce travail de recherche a donc permis de mettre en évidence les domaines de la prévention encore insuffisamment proposés aux patients et de rendre attentif le personnel médical sur le fait qu'il existe en Suisse des groupes de personnes qui reçoivent moins de prévention que d'autres groupes. Dans le futur, l'accent devrait être d'avantage mis durant les études de médecine et lors de la formation post-graduée sur les mesures préventives pas assez exploitées en Suisse en particulier le dépistage des cancers et la vaccination annuelle contre la grippe.

Ongoing and future developments at the Universal Protein Resource.

The primary mission of Universal Protein Resource (UniProt) is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 4 weeks and can be accessed online for searches or download at http://www.uniprot.org.

Genometric analyses of the organization of circular chromosomes: a universal pressure determines the direction of ribosomal RNA genes transcription relative to chromosome replication.

Selective pressures related to gene function and chromosomal architecture are acting on genome sequences and can be revealed, for instance, by appropriate genometric methods. Cumulative nucleotide skew analyses, i.e., GC, TA, and ORF orientation skews, predict the location of the origin of DNA replication for 88 out of 100 completely sequenced bacterial chromosomes. These methods appear fully reliable for proteobacteria, Gram-positives, and spirochetes as well as for euryarchaeotes. Based on this genome architecture information, coorientation analyses reveal that in prokaryotes, ribosomal RNA (rRNA) genes encoding the small and large ribosomal subunits are all transcribed in the same direction as DNA replication; that is, they are located along the leading strand. This result offers a simple and reliable method for circumscribing the region containing the origin of the DNA replication and reveals a strong selective pressure acting on the orientation of rRNA genes similar to the weaker one acting on the orientation of ORFs. Rate of coorientation of transfer RNA (tRNA) genes with DNA replication appears to be taxon-specific. Analyzing nucleotide biases such as GC and TA skews of genes and plotting one against the other reveals a taxonomic clusterization of species. All ribosomal RNA genes are enriched in Gs and depleted in Cs, the only so far known exception being the rRNA genes of deuterostomian mitochondria. However, this exception can be explained by the fact that in the chromosome of the human mitochondrion, the model of the deuterostomian organelle genome, DNA replication, and rRNA transcription proceed in opposite directions. A general rule is deduced from prokaryotic and mitochondrial genomes: ribosomal RNA genes that are transcribed in the same direction as the DNA replication are enriched in Gs, and those transcribed in the opposite direction are depleted in Gs.

Benefit of Cup Medialization in Total Hip Arthroplasty is Associated With Femoral Anatomy.

BACKGROUND: Medialization of the cup with a respective increase in femoral offset has been proposed in THA to increase abductor moment arms. Insofar as there are potential disadvantages to cup medialization, it is important to ascertain whether the purported biomechanical benefits of cup medialization are large enough to warrant the downsides; to date, studies regarding this question have disagreed. QUESTIONS/PURPOSES: The purpose of this study was to quantify the effect of cup medialization with a compensatory increase in femoral offset compared with anatomic reconstruction for patients undergoing THA. We tested the hypothesis that there is a (linear) correlation between preoperative anatomic parameters and muscle moment arm increase caused by cup medialization. METHODS: Fifteen patients undergoing THA were selected, covering a typical range of preoperative femoral offsets. For each patient, a finite element model was built based on a preoperative CT scan. The model included the pelvis, femur, gluteus minimus, medius, and maximus. Two reconstructions were compared: (1) anatomic position of the acetabular center of rotation, and (2) cup medialization compensated by an increase in the femoral offset. Passive abduction-adduction and flexion-extension were simulated in the range of normal gait. Muscle moment arms were evaluated and correlated to preoperative femoral offset, acetabular offset, height of the greater trochanter (relative to femoral center of rotation), and femoral antetorsion angle. RESULTS: The increase of muscle moment arms caused by cup medialization varied among patients. Muscle moment arms increase by 10% to 85% of the amount of cup medialization for abduction-adduction and from -35% (decrease) to 50% for flexion-extension. The change in moment arm was inversely correlated (R(2) = 0.588, p = 0.001) to femoral antetorsion (anteversion), such that patients with less femoral antetorsion gained more in terms of hip muscle moments. No linear correlation was observed between changes in moment arm and other preoperative parameters in this series. CONCLUSIONS: The benefit of cup medialization is variable and depends on the individual anatomy. CLINICAL RELEVANCE: Cup medialization with compensatory increase of the femoral offset may be particularly effective in patients with less femoral antetorsion. However, cup medialization must be balanced against its tradeoffs, including the additional loss of medial acetabular bone stock, and eventual proprioceptive implications of the nonanatomic center of rotation and perhaps joint reaction forces. Clinical studies should better determine the relevance of small changes of moment arms on function and joint reaction forces.

Social and medical vulnerability factors of emergency department frequent users in a universal health insurance system.

OBJECTIVES: The objectives were to identify the social and medical factors associated with emergency department (ED) frequent use and to determine if frequent users were more likely to have a combination of these factors in a universal health insurance system. METHODS: This was a retrospective chart review case-control study comparing randomized samples of frequent users and nonfrequent users at the Lausanne University Hospital, Switzerland. The authors defined frequent users as patients with four or more ED visits within the previous 12 months. Adult patients who visited the ED between April 2008 and March 2009 (study period) were included, and patients leaving the ED without medical discharge were excluded. For each patient, the first ED electronic record within the study period was considered for data extraction. Along with basic demographics, variables of interest included social (employment or housing status) and medical (ED primary diagnosis) characteristics. Significant social and medical factors were used to construct a logistic regression model, to determine factors associated with frequent ED use. In addition, comparison of the combination of social and medical factors was examined. RESULTS: A total of 359 of 1,591 frequent and 360 of 34,263 nonfrequent users were selected. Frequent users accounted for less than a 20th of all ED patients (4.4%), but for 12.1% of all visits (5,813 of 48,117), with a maximum of 73 ED visits. No difference in terms of age or sex occurred, but more frequent users had a nationality other than Swiss or European (n = 117 [32.6%] vs. n = 83 [23.1%], p = 0.003). Adjusted multivariate analysis showed that social and specific medical vulnerability factors most increased the risk of frequent ED use: being under guardianship (adjusted odds ratio [OR] = 15.8; 95% confidence interval [CI] = 1.7 to 147.3), living closer to the ED (adjusted OR = 4.6; 95% CI = 2.8 to 7.6), being uninsured (adjusted OR = 2.5; 95% CI = 1.1 to 5.8), being unemployed or dependent on government welfare (adjusted OR = 2.1; 95% CI = 1.3 to 3.4), the number of psychiatric hospitalizations (adjusted OR = 4.6; 95% CI = 1.5 to 14.1), and the use of five or more clinical departments over 12 months (adjusted OR = 4.5; 95% CI = 2.5 to 8.1). Having two of four social factors increased the odds of frequent ED use (adjusted = OR 5.4; 95% CI = 2.9 to 9.9), and similar results were found for medical factors (adjusted OR = 7.9; 95% CI = 4.6 to 13.4). A combination of social and medical factors was markedly associated with ED frequent use, as frequent users were 10 times more likely to have three of them (on a total of eight factors; 95% CI = 5.1 to 19.6). CONCLUSIONS: Frequent users accounted for a moderate proportion of visits at the Lausanne ED. Social and medical vulnerability factors were associated with frequent ED use. In addition, frequent users were more likely to have both social and medical vulnerabilities than were other patients. Case management strategies might address the vulnerability factors of frequent users to prevent inequities in health care and related costs.

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

BACKGROUND AND PURPOSE: We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received IV thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. RESULTS: In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS: IV thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients.

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

Introducing systematic dispatcher-assisted cardiopulmonary resuscitation (telephone-CPR) in a non-Advanced Medical Priority Dispatch System (AMPDS): implementation process and costs.

OBJECTIVE: In order to improve the quality of our Emergency Medical Services (EMS), to raise bystander cardiopulmonary resuscitation rates and thereby meet what is becoming a universal standard in terms of quality of emergency services, we decided to implement systematic dispatcher-assisted or telephone-CPR (T-CPR) in our medical dispatch center, a non-Advanced Medical Priority Dispatch System. The aim of this article is to describe the implementation process, costs and results following the introduction of this new "quality" procedure. METHODS: This was a prospective study. Over an 8-week period, our EMS dispatchers were given new procedures to provide T-CPR. We then collected data on all non-traumatic cardiac arrests within our state (Vaud, Switzerland) for the following 12months. For each event, the dispatchers had to record in writing the reason they either ruled out cardiac arrest (CA) or did not propose T-CPR in the event they did suspect CA. All emergency call recordings were reviewed by the medical director of the EMS. The analysis of the recordings and the dispatchers' written explanations were then compared. RESULTS: During the 12-month study period, a total of 497 patients (both adults and children) were identified as having a non-traumatic cardiac arrest. Out of this total, 203 cases were excluded and 294 cases were eligible for T-CPR. Out of these eligible cases, dispatchers proposed T-CPR on 202 occasions (or 69% of eligible cases). They also erroneously proposed T-CPR on 17 occasions when a CA was wrongly identified (false positive). This represents 7.8% of all T-CPR. No costs were incurred to implement our study protocol and procedures. CONCLUSIONS: This study demonstrates it is possible, using a brief campaign of sensitization but without any specific training, to implement systematic dispatcher-assisted cardiopulmonary resuscitation in a non-Advanced Medical Priority Dispatch System such as our EMS that had no prior experience with systematic T-CPR. The results in terms of T-CPR delivery rate and false positive are similar to those found in previous studies. We found our results satisfying the given short time frame of this study. Our results demonstrate that it is possible to improve the quality of emergency services at moderate or even no additional costs and this should be of interest to all EMS that do not presently benefit from using T-CPR procedures. EMS that currently do not offer T-CPR should consider implementing this technique as soon as possible, and we expect our experience may provide answers to those planning to incorporate T-CPR in their daily practice.

Stroke initial severity and outcome relative to insurance status in a universal health care system in Switzerland.

BACKGROUND:  Socioeconomic status is thought to have a significant influence on stroke incidence, risk factors and outcome. Its influence on acute stroke severity, stroke mechanisms, and acute recanalisation treatment is less known. METHODS:  Over a 4-year period, all ischaemic stroke patients admitted within 24 h were entered prospectively in a stroke registry. Data included insurance status, demographics, risk factors, time to hospital arrival, initial stroke severity (NIHSS), etiology, use of acute treatments, short-term outcome (modified Rankin Scale, mRS). Private insured patients (PI) were compared with basic insured patients (BI). RESULTS:  Of 1062 consecutive acute ischaemic stroke patients, 203 had PI and 859 had BI. They were 585 men and 477 women. Both populations were similar in age, cardiovascular risk factors and preventive medications. The onset to admission time, thrombolysis rate, and stroke etiology according to TOAST classification were not different between PI and BI. Mean NIHSS at admission was significantly higher for BI. Good outcome (mRS ≤ 2) at 7 days and 3 months was more frequent in PI than in BI. CONCLUSION:  We found better outcome and lesser stroke severity on admission in patients with higher socioeconomic status in an acute stroke population. The reason for milder strokes in patients with better socioeconomic status in a universal health care system needs to be explained.