Purpose The aim of this study was to update reference data of handgrip strength for healthy adults of both genders spanning a wide age range and to analyze possible factors of influence. Methods ...Intraindividual and interindividual variations of grip strength and their relation to several anthropometric factors were analyzed in a standardized manner for 769 healthy adults (women, n = 403; men, n = 366) aged between 20 years and 95 years. Measurements were done in neutral position of arm, forearm, and wrist on setting II of a Baseline digital hydraulic dynamometer (NexGen Ergonomics Inc. Quebec, Canada). Results Mean strength was about 41% less in women (right 29 kg; left 27 kg) than in men (right 49 kg; left 47 kg) resulting in a ratio of left to right hand slightly above .95 in both genders. During the course of life, hand strength develops comparably in both genders peaking at 35 years of age and decreasing continuously further on. Anthropometric variables such as forearm circumference and length, hand size, or body mass showed a positive correlation with grip strength. Body mass index, type of work, and hand dominance showed only a partial positive correlation or no correlation with grip strength. Gender and age, followed by parameters representing body length and obesity, were observed to have the highest predictive value for handgrip strength and were therefore entered into the generation of prediction equations. Conclusions We recommend side adjustment of measured values for intraindividual comparison and inclusion of information regarding anthropometric characteristics, as well as using gender- and age-adjusted reference values, whereas hand dominance can be neglected. The regression equations we generated might prove to be useful for clinicians or for those who use normative values within software to provide more accurate predictions of strength scores for specific applications.
ObjectivesOncologists need competence in clinical prognostication to deliver appropriate care to patients with cancer. Most studies on prognostication have been restricted to patients in palliative ...care settings. This paper investigates (1) the prognostic accuracy of physicians regarding a broad cohort of patients with cancer with a median life expectancy of >2 years and (2) whether a prognosis training can improve prognostication.DesignProspective single-centre study comprising 3 phases, each lasting 1 month.SettingLarge teaching hospital, department of oncology and haematology, Germany.Participants18 physicians with a professional experience from entry level to 34 years. 736 patients with oncological and malignant haematological diseases.InterventionsBaseline prognostication abilities were recorded during an ‘untrained’ phase 1. As an intervention, a specific prognosis-training programme was implemented prior to phases 2 and 3. In phase 3, physicians had to provide additional estimates with the inclusion of electronic prognostic tools.Outcome measuresPrognostic estimates (PE) were collected using ‘standard’ surprise question (SQ), ‘probabilistic’ SQ (both for short-term prognostication up to 6 months) and clinician prediction of survival (CPS) (for long-term prognostication). Estimated prognoses were compared with observed survival. Phase 1 was compared with phases 2 and 3.ResultsWe included 2427 PE for SQ, 1506 for CPS and 800 for probabilistic SQ. Median OS was 2.5 years. SQ accuracy improved significantly (p<0.001) from 72.6% in phase 1 to 84.3% in phase 3. Probabilistic SQ in phase 3 showed 83.1% accuracy. CPS accuracy was 25.9% and could not be significantly improved. (Electronic) prognostic tools—used alone—performed significantly worse (p<0.0005) than physicians and—used by the clinicians—did not improve their performance.ConclusionA specific prognosis-training programme could improve short-term and intermediate-term prognostication. Improvement of long-term prognostication was not possible. Inexperienced residents as well as experienced oncologists benefited from training.
Chemical denaturant titrations can be used to accurately determine protein stability. However, data acquisition is typically labour intensive, has low throughput and is difficult to automate. These ...factors, combined with high protein consumption, have limited the adoption of chemical denaturant titrations in commercial settings. Thermal denaturation assays can be automated, sometimes with very high throughput. However, thermal denaturation assays are incompatible with proteins that aggregate at high temperatures and large extrapolation of stability parameters to physiological temperatures can introduce significant uncertainties. We used capillary-based instruments to measure chemical denaturant titrations by intrinsic fluorescence and microscale thermophoresis. This allowed higher throughput, consumed several hundred-fold less protein than conventional, cuvette-based methods yet maintained the high quality of the conventional approaches. We also established efficient strategies for automated, direct determination of protein stability at a range of temperatures via chemical denaturation, which has utility for characterising stability for proteins that are difficult to purify in high yield. This approach may also have merit for proteins that irreversibly denature or aggregate in classical thermal denaturation assays. We also developed procedures for affinity ranking of protein–ligand interactions from ligand-induced changes in chemical denaturation data, and proved the principle for this by correctly ranking the affinity of previously unreported peptide–PDZ domain interactions. The increased throughput, automation and low protein consumption of protein stability determinations afforded by using capillary-based methods to measure denaturant titrations, can help to revolutionise protein research. We believe that the strategies reported are likely to find wide applications in academia, biotherapeutic formulation and drug discovery programmes.
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•Chemical denaturant titrations are slow, lengthy and consume lots of protein sample.•We developed very fast methods for measuring chemical denaturant titrations.•Automated titrations can be measured in minutes using only μl sample volumes.•Ligand interactions rapidly screened and ranked via changes in protein stability•These advances make chemical denaturation more suitable for commercial research.
HBc, the capsid-forming “core protein” of human hepatitis B virus (HBV), is a multidomain, α-helical homodimer that aggressively forms human HBV capsids. Structural plasticity has been proposed to be ...important to the myriad functions HBc mediates during viral replication. Here, we report detailed thermodynamic analyses of the folding of the dimeric HBc protomer under conditions that prevented capsid formation. Central to our success was the use of ion mobility spectrometry–mass spectrometry and microscale thermophoresis, which allowed folding mechanisms to be characterized using just micrograms of protein. HBc folds in a three-state transition with a stable, dimeric, α-helical intermediate. Extensive protein engineering showed thermodynamic linkage between different structural domains. Unusual effects associated with mutating some residues suggest structural strain, arising from frustrated contacts, is present in the native dimer. We found evidence of structural gatekeepers that, when mutated, alleviated native strain and prevented (or significantly attenuated) capsid formation by tuning the population of alternative native conformations. This strain is likely an evolved feature that helps HBc access the different structures associated with its diverse essential functions. The subtle balance between native and strained contacts may provide the means to tune conformational properties of HBc by molecular interactions or mutations, thereby conferring allosteric regulation of structure and function. The ability to trap HBc conformers thermodynamically by mutation, and thereby ablate HBV capsid formation, provides proof of principle for designing antivirals that elicit similar effects.
Abstract
Background
Multidisciplinary biopsychosocial rehabilitation (MBR) in patients with chronic low back pain (CLBP) is superior to less intensive treatments for at least one year, but the ...long-term course of the disease is largely unknown. The primary aim of this study was to describe the long-term course of an MBR in relation to pain, disability, and quality of life from the beginning of an MBR to between 4 to 15 years after participation. The secondary aim was to explore the long-term course of an MBR in relation to physiological outcomes of functioning.
Methods
This was a observational study conducted at a university hospital. The cohort consisted of participants of a 3-week, CLBP-specific MBR program between August 2001 and January 2013. The North American Spine Society questionnaire (NASS) pain and disability scale was the primary patient -reported outcome measure (PROM). The NASS neurogenic symptoms scale and the Short-Form 36 (SF-36) health survey were secondary PROMs. Patients were assessed before entry to the MBR (T0), at entry (T1), at discharge (T2) and 4 to 15 years after discharge (T3). Effects were quantified by effect size (ES). Score differences were tested for significance using parametric or non-parametric tests and linear mixed models.
Results
Of 299 consecutive patients from the MBR program, 229 could be contacted. Of these, 84 declined participation, five did not meet the inclusion criteria, and 26 had incomplete data. Thus, 114 patients were included. The mean follow-up time was 9.2 years. At T3, patients exhibited beneficial effects for NASS pain and disability with a moderate ES (ES = 0.63;
p
< 0.001). The NASS neurogenic symptoms scale was stable. The SF-36 scales showed an improvement in the bodily pain domain (ES = 1.02;
p
< 0.001), but no significant changes for physical functioning, physical role, general health, vitality, social functioning, emotional role, or mental health. The physical health component summary was improved (ES = 0.40,
p
= 0.002), and the mental health summary was unchanged. The linear mixed model analysis confirmed improvements in pain and disability between T1 and T3 (
p
= 0.010).
Conclusions
The results of this study suggest that there is a long-term benefit of MBR participation in patients with CLBP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several studies have assessed predictors of weaning and extubation outcome in short-term mechanically ventilated patients, but there are only few studies on predictors of weaning from prolonged ...mechanical ventilation.
Retrospective, single-center, observational study at a specialized national weaning center in Germany. Patients' medical records were reviewed to obtain data on demographics, comorbidities, respiratory indices, and the result of a prospectively documented, standardized spontaneous breathing trial (SBT) upon admission to the weaning center. Respiratory indices assessed were the ventilatory ratio (VR) and parameters derived from calculated mechanical power (MP). Predictors associated with failure of prolonged weaning and failure of the SBT were assessed using a binary logistic regression model.
A total of 263 prolonged mechanically ventilated, tracheotomized patients, treated over a 5-year period were analyzed. After 3 weeks of mechanical ventilation, patients with unsuccessful weaning failed a SBT more frequently and showed significantly increased values for inspiratory positive airway pressure, driving pressure, VR, absolute MP, and MP normalized to predicted body weight and dynamic lung-thorax compliance (LTC-MP). In the logistic regression analyses, variables independently correlated with weaning failure were female gender (adjusted odds ratio 0.532 95% CI 0.291-0.973;
= 0.040), obesity (body mass index ≥ 30 kg/m
) (2.595 1.210-5.562;
= 0.014), COPD (3.209 1.563-6.589;
= 0.002), LTC-MP (3.470 1.067-11.284;
= 0.039), P
CO
on mechanical ventilation (1.101 95% CI 1.034-1.173;
= 0.003), and failure of the SBT (4.702 2.250-9.825;
< 0.001). In addition, female gender (0.401 0.216-0.745;
= 0.004), LTC-MP (3.017 1.027-8.862;
= 0.046), and P
CO
on mechanical ventilation (1.157 1.083-1.235;
< 0.001) were independent risk factors for an unsuccessful SBT.
In the present study, the derived predictors of weaning point to a crucial role of the workload imposed on respiratory muscles during spontaneous breathing. Mechanical power normalized to lung-thorax compliance was independently correlated with weaning outcome and may identify patients at high risk for weaning failure.
OBJECTIVE Sinus-preserving (SP) embolization techniques augment endovascular treatment options for intracranial lateral dural arteriovenous fistulas (DAVFs). The authors aimed to perform a ...retrospective comparison of their primary success rates, complication rates, and long-term follow-up with those of sinus-occluding (SO) treatment variants in the collective of low- and intermediate-grade lateral DAVFs (Cognard Types I-IIb). METHODS Clinical symptoms, complication rates, and Cognard grading prior to and after endovascular DAVF treatment using different technical approaches was retrospectively analyzed in 36 patients with lateral DAVF Cognard Types I-IIb. The long-term success rate was determined by a standardized questionnaire. RESULTS The SO approaches offered a higher rate of definitive fistula occlusion (93% SO vs 71% SP) but were accompanied by a significantly higher complication rate (33% or 20% SO vs 0% SP). The patients interviewed reported very high satisfaction with their health in long-term follow-up in both groups. CONCLUSIONS A higher rate of definitive fistula occlusion in the SO group was attained at the price of a significantly higher complication rate. The SP approaches offered a good primary success rate in combination with a very low complication rate. Despite some limitations of the data (e.g., a small sample size) the authors thus recommend an SP variant as the primary therapeutic option for the endovascular treatment of low- and intermediate-grade DAVFs. The SO approaches should be restricted to cases in which SP treatment does not achieve a downgrading to no worse than Cognard Type IIa.
Current screening algorithms for type 2 diabetes (T2D) rely on fasting plasma glucose (FPG) and/or HbA1c. This fails to identify a sizeable subgroup of individuals in early stages of metabolic ...dysregulation who are at high risk for developing diabetes or cardiovascular disease. The Matsuda index, a combination of parameters derived from a fasting and postprandial insulin assay, is an early biomarker for metabolic dysregulation (i.e. insulin resistance/compensatory hyperinsulinemia). The aim of this analysis was to compare four widely available anthropometric and biochemical markers indicative of this condition waist-to-height ratio (WHtR), hypertriglyceridemic-waist phenotype (HTW), triglycerides-to-HDL-C ratio (TG/HDL-C) and FPG to the Matsuda index. This cross-sectional analysis included 2231 individuals with normal fasting glucose (NFG, n = 1333), impaired fasting glucose (IFG, n = 599) and T2D (n = 299) from an outpatient diabetes clinic in Germany and thus extended a prior analysis from our group done on the first two subgroups. We analyzed correlations of the Matsuda index with WHtR, HTW, TG/HDL-C and FPG and their predictive accuracies by correlation and logistic regression analyses and receiver operating characteristics. In the entire group and in NFG, IFG and T2D, the best associations were observed between the Matsuda index and the WHtR (r = - 0.458), followed by HTW phenotype (r = - 0.438). As for prediction accuracy, WHtR was superior to HTW, TG/HDL-C and FPG in the entire group (AUC 0.801) and NFG, IFG and T2D. A multivariable risk score for the prediction of insulin resistance was tested and demonstrated an area under the ROC curve of 0.765 for WHtR and its interaction with sex as predictor controlled by age and sex. The predictive power increased to 0.845 when FPG and TG/HDL-C were included. Using as a comparator the Matsuda index, WHtR, compared to HTW, TG/HDL-C and FPG, showed the best predictive value for detecting metabolic dysregulation. We conclude that WHtR, a widely available anthropometric index, could refine phenotypic screening for insulin resistance/hyperinsulinemia. This may ameliorate early identification of individuals who are candidates for appropriate therapeutic interventions aimed at addressing the twin epidemic of metabolic and cardiovascular disease in settings where more extended testing such as insulin assays are not feasible.
This study aimed to evaluate the shear bond strength (SBS) and microleakage of a new self-etch adhesive-based fissure sealant (EG) on aprismatic enamel in comparison to conventional fissure sealing ...with 30 s acid etching (CG). The fissures were sealed according to the manufacturer’s instructions. Each group was divided into 3 subgroups: 1-day water storage, 3-month water storage, and 5,000× thermocycling. After measuring SBS using the Ultradent method, failure mode was analyzed. In additional 16 teeth, microleakage was tested using dye penetration method. Pairwise comparisons were analyzed using Mann-Whitney U-Test. Multiple linear regression was performed to assess the factors influencing on SBS. EG had significantly lower mean SBS (4.1 MPa±2.1) than the CG (17.6 MPa±6.4). CG (1.1%) performed significantly better than the EG (12.8%) in microleakage analysis. The tested EG yielded significantly inferior results and its clinical use should be decided after weighing its pros and cons.
Objective To evaluate the association between serum P levels on the day of hCG administration and pregnancy outcome in women undergoing controlled ovarian hyperstimulation, prevention of premature ...ovulation by GnRH analogues, and fresh ET after 5 days of embryo culture. Design Retrospective, observational, cohort study. Setting Private IVF center. Patient(s) A total of 2,555 women undergoing fresh ET on day 5 in 2,062 GnRH agonist and 493 GnRH antagonist cycles. Intervention(s) None. Main Outcome Measure(s) Live birth rate. Result(s) Live birth rate in cycles with GnRH agonists was significantly lower in women with P levels ≥2.0 ng/mL (17.4%) on the day of hCG administration as compared with women with P levels <1.5 ng/mL (24.6%) and 1.5–1.99 ng/mL (26.7%). No such significant differences in live birth rates in cycles with GnRH antagonist could be observed. Conclusion(s) A rise of serum P levels ≥2.0 ng/mL on the day of hCG administration is associated with impaired early embryo implantation and reduced live birth rate in cycles with GnRH agonists after day-5 fresh ET. Clinical Trial Registration Number NCT01426152.
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