Biomarker zur Früherkennung obligater Präkanzerosen der Mundschleimhaut mittels „Brush“- Zytologie

Ziel der vorliegenden Studie war die Erarbeitung einer nicht- invasiven und objektiven Methode zur Risikoabschätzung für Karzinomentstehung in der Mundhöhle. Übergeordnetes Ziel war es, mögliche Biomarker zur Karzinogenese oder als Prognoseparameter für intraorale Karzinome zu identifizieren. In dieser Studie wurden zytologische und DNA-zytometrische Untersuchungen durchgeführt an mittels Brush- Biopsie gewonnenen Mundschleimhautproben von 10 gesunden Probanden, 17 Patienten mit Leukoplakien und 10 Patienten mit manifesten Mundhöhlenkarzinomen

Optimising surface roughness and density in titanium fabrication via laser powder bed fusion

The Ti6Al4V alloy has many advantages, such as being lightweight, formal, and resistant to corrosion. This makes it highly desirable for various applications, especially in the aerospace industry. Laser Powder Bed Fusion (LPBF) is a technique that allows for the production of detailed and unique parts with great flexibility in design. However, there are challenges when it comes to achieving high-quality surfaces and porosity formation in the material, which limits the wider use of LPBF. To tackle these challenges, this study uses statistical techniques called Design of Experiments (DoE) and Analysis of Variance (ANOVA) to investigate and optimise the process parameters of LPBF for making Ti6Al4V components with improved density and surface finish. The parameters examined in this study are laser power, laser scan speed, and hatch space. The optimisation study results show that using specific laser settings, like a laser power of 175 W, a laser scan speed of 1914 mm/s, and a hatch space of 53 µm, produces Ti6Al4V parts with a high relative density of 99.54% and low top and side surface roughness of 2.6 µm and 4.3 µm, respectively. This promising outcome demonstrates the practicality of optimising Ti6Al4V and other metal materials for a wide range of applications, thereby overcoming existing limitations and further expanding the potential of LPBF while minimising inherent process issues

Hybrid finite element–smoothed particle hydrodynamics modelling for optimizing cutting parameters in CFRP composites

Carbon-fibre-reinforced plastic (CFRP) is increasingly being used in various applications including aerospace, automotive, wind energy, sports, and robotics, which makes the precision modelling of its machining operations a critical research area. However, the classic finite element modelling (FEM) approach has limitations in capturing the complexity of machining, particularly with regard to the interaction between the fibre–matrix interface and the cutting edge. To overcome this limitation, a hybrid approach that integrates smoothed particle hydrodynamics (SPHs) with FEM was developed and tested in this study. The hybrid FEM-SPH approach was compared with the classic FEM approach and validated with experimental measurements that took into account the cutting tool’s round edge. The results showed that the hybrid FEM-SPH approach outperformed the classic FEM approach in predicting the thrust force and bounce back of CFRP machining due to the integrated cohesive model and the element conversion after failure in the developed approach. The accurate representation of the fibre–matrix interface in the FEM-SPH approach resulted in predicting precise chip formation in terms of direction and morphology. Nonetheless, the computing time of the FEM-SPH approach is higher than the classic FEM. The developed hybrid FEM-SPH model is promising for improving the accuracy of simulation in machining processes, combining the benefits of both techniques

Chip formation and orthogonal cutting optimisation of unidirectional carbon fibre composites

This study presents a thorough experimental investigation utilising the design of experiments and analysis of variance (ANOVA) to examine the impact of machining process parameters on chip formation mechanisms, machining forces, workpiece surface integrity, and damage resulting from the orthogonal cutting of unidirectional CFRP. The study identified the mechanisms behind chip formation and found it to significantly impact the workpiece orientation of fibre and the tool’s cutting angle, resulting in increased fibre bounceback at larger fibre orientation angles and when using smaller rake angle tools. Increasing the depth of cut and fibre orientation angle results in an increased damage depth, while using higher rake angles reduces it. An analytical model based on response surface analysis for predicting machining forces, damage, surface roughness, and bounceback was also developed. The ANOVA results indicate that fibre orientation is the most significant factor in machining CFRP, while cutting speed is insignificant. Increasing fibre orientation angle and depth leads to deeper damage, while larger tool rake angles re-duce damage. Machining workpieces with 0° fibre orientation angle results in the least subsurface damage, and surface roughness is unaffected by the tool rake angle for fibre orientations between 0° to 90° but worsens for angles greater than 90°. Optimisation of cutting parameters were subsequently optimised to improve machined workpiece surface quality and reduce forces. The experimental results showed that negative rake angle and cutting at moderately low speeds (366 mm/min) is the optimal conditions for machining laminates with a fibre angle of θ = 45°. On the other hand, for composite materials with fibre angles of θ = 90° and θ = 135°, it is recommended to use a high positive rake angle and cutting speeds

LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse

Premature ovarian failure and female infertility are frequent side effects of anticancer therapies, owing to the extreme sensitivity of the ovarian reserve oocytes to the damaging effects of irradiation and chemotherapy on DNA. We report here a robust protective effect of luteinizing hormone (LH) on the primordial follicle pool of prepubertal ovaries against the cisplatin (Cs)-induced apoptosis. In vitro LH treatment of prepubertal ovarian fragments generated anti-apoptotic signals by a subset of ovarian somatic cells expressing LH receptor (LHR) through cAMP/PKA and Akt pathways. Such signals, reducing the oocyte level of pro-apoptotic TAp63 protein and favoring the repair of the Cs-damaged DNA in the oocytes, prevented their apoptosis. Noteworthy, in vivo administration to prepubertal female mice of a single dose of LH together with Cs inhibited the depletion of the primordial follicle reserve caused by the drug and preserved their fertility in reproductive age, preventing significant alteration in the number of pregnancy and of delivered pups. In conclusion, these findings establish a novel ovoprotective role for LH and further support the very attracting prospective to use physiological 'fertoprotective' approaches for preventing premature infertility and risks linked to precocious menopause in young patients who survived cancer after chemotherapy

Effects of plasma magnesium and prolactin on quantitative ultrasound measurements of heel bone among schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is a bone disease that can reduce both bone mass and bone strength. It can cause serious fractures of bones, along with causing significant and even devastating physical, psychological and financial consequences for patients and their family members. Many reports have revealed that the prevalence of decreased bone density is higher in schizophrenic patients than in the non-psychological diseased population. The previous report of our group revealed that chronic schizophrenia patients have poorer BUA levels since they were young as compared to the general community population. Hyperprolactinemia and antipsychotics are reported to be among the risk factors for osteoporosis in chronic schizophrenic patients.</p> <p>Methods</p> <p>93 schizophrenic patients with severely poor adjusted BUA values and 93 age and gender matched patients with normal adjusted BUA values from a previous survey study were selected. Data were collected via questionnaires and via reviews of antipsychotic medications. Blood samples were drawn, and serum levels of prolactin, estradiol, testosterone, magnesium, calcium, phosphate, osteocalcin, Cross-linked N-teleopeptide of type I collagen (NTX), thyroid hormone and parathyroid hormone were checked. The association between BUA levels and serum levels of the above items, along with the type of received antipsychotic medication, was evaluated.</p> <p>Results</p> <p>There was no significant association found between reduced BUA levels and serum prolactin, calcium, phosphate, osteocalcin, NTX, thyroid stimulating hormone and parathyroid hormone levels. There was also no association between BUA levels and types of currently received antipsychotics. There was no association between BUA levels and menstruation condition in female patients. Hypermagnesemia had a borderline association with classical and combined (classical and atypical) antipsychotic medications in male patients. Nevertheless, hypermagnesemia is a significant protective factor of reduced BUA levels in female patients. Hyperprolactinemia had a significant association with classical and combined antipsychotic medications in female patients. Hyperprolactinemia, however, provides a protective effect on reduced BUA levels in male patients. There was no significant association found between serum prolactin level and the type of antipsychotic medication received.</p> <p>Conclusions</p> <p>The results of this study are in contrast with literature that has reported an association between bone mass and serum prolactin levels, serum magnesium levels and type of received antipsychotics. Further study to investigate the pathophysiological process and the association between bone mass and serum prolactin level, serum magnesium level and specific antipsychotics is necessary.</p

Bone mass in schizophrenia and normal populations across different decades of life

<p>Abstract</p> <p>Background</p> <p>Chronic schizophrenic patients have been reported as having higher osteoporosis prevalence. Survey the bone mass among schizophrenic patients and compare with that of the local community population and reported data of the same country to figure out the distribution of bone mass among schizophrenic patients.</p> <p>Methods</p> <p>965 schizophrenic patients aged 20 years and over in Yuli Veterans Hospital and 405 members aged 20 and over of the community living in the same town as the institute received bone mass examination by a heel qualitative ultrasound (QUS) device. Bone mass distribution was stratified to analyzed and compared with community population.</p> <p>Results</p> <p>Schizophrenic patients have lower bone mass while they are young. But aging effect on bone mass cannot be seen. Accelerated bone mass loss during menopausal transition was not observed in the female schizophrenic patients as in the subjects of the community female population.</p> <p>Conclusion</p> <p>Schizophrenic patients have lower bone mass than community population since they are young. Further study to investigate the pathophysiological process is necessary to delay or avoid the lower bone mass in schizophrenia patients.</p

Revealing Dissociable Attention Biases in Chronic Smokers Through an Individual-Differences Approach

Addiction is accompanied by attentional biases (AB), wherein drug-related cues grab attention independently of their perceptual salience. AB have emerged in different flavours depending on the experimental approach, and their clinical relevance is still debated. In chronic smokers we sought evidence for dissociable attention abnormalities that may play distinct roles in the clinical manifestations of the disorder. Fifty smokers performed a modified visual probe-task measuring two forms of AB and their temporal dynamics, and data on their personality traits and smoking history/ status were collected. Two fully dissociable AB effects were found: A Global effect, reflecting the overall impact of smoke cues on attention, and a Location-specific effect, indexing the impact of smoke cues on visuospatial orienting. Importantly, the two effects could be neatly separated from one another as they: (i) unfolded with dissimilar temporal dynamics, (ii) were accounted for by different sets of predictors associated with personality traits and smoking history and (iii) were not correlated with one another. Importantly, the relevance of each of these two components in the single individual depends on a complex blend of personality traits and smoking habits, a result that future efforts addressing the clinical relevance of addiction-related AB should take into careful consideration.This study was supported by funding provided by the University of Verona to CDL, CC and L

Nicotine preloading for smoking cessation: the Preloading RCT

Background: Nicotine preloading means using nicotine replacement therapy prior to a quit date while smoking normally. The aim is to reduce the drive to smoke, thereby reducing cravings for smoking after quit day, which are the main cause of early relapse. A prior systematic review showed inconclusive and heterogeneous evidence that preloading was effective and little evidence of the mechanism of action, with no cost-effectiveness data. Objectives: To assess (1) the effectiveness, safety and tolerability of nicotine preloading in a routine NHS setting relative to usual care, (2) the mechanisms of the action of preloading and (3) the cost-effectiveness of preloading. Design: Open-label randomised controlled trial with examination of mediation and a cost-effectiveness analysis. Setting: NHS smoking cessation clinics. Participants: People seeking help to stop smoking. Interventions: Nicotine preloading comprised wearing a 21 mg/24 hour nicotine patch for 4 weeks prior to quit date. In addition, minimal behavioural support was provided to explain the intervention rationale and to support adherence. In the comparator group, participants received equivalent behavioural support. Randomisation was stratified by centre and concealed from investigators. Main outcome measures: The primary outcome was 6-month prolonged abstinence assessed using the Russell Standard. The secondary outcomes were 4-week and 12-month abstinence. Adverse events (AEs) were assessed from baseline to 1 week after quit day. In a planned analysis, we adjusted for the use of varenicline (Champix®; Pfizer Inc., New York, NY, USA) as post-cessation medication. Cost-effectiveness analysis took a health-service perspective. The within-trial analysis assessed health-service costs during the 13 months of trial enrolment relative to the previous 6 months comparing trial arms. The base case was based on multiple imputation for missing cost data. We modelled long-term health outcomes of smoking-related diseases using the European-study on Quantifying Utility of Investment in Protection from Tobacco (EQUIPT) model. Results: In total, 1792 people were eligible and were enrolled in the study, with 893 randomised to the control group and 899 randomised to the intervention group. In the intervention group, 49 (5.5%) people discontinued preloading prematurely and most others used it daily. The primary outcome, biochemically validated 6-month abstinence, was achieved by 157 (17.5%) people in the intervention group and 129 (14.4%) people in the control group, a difference of 3.02 percentage points [95% confidence interval (CI) –0.37 to 6.41 percentage points; odds ratio (OR) 1.25, 95% CI 0.97 to 1.62; p = 0.081]. Adjusted for use of post-quit day varenicline, the OR was 1.34 (95% CI 1.03 to 1.73; p = 0.028). Secondary abstinence outcomes were similar. The OR for the occurrence of serious AEs was 1.12 (95% CI 0.42 to 3.03). Moderate-severity nausea occurred in an additional 4% of the preloading group compared with the control group. There was evidence that reduced urges to smoke and reduced smoke inhalation mediated the effect of preloading on abstinence. The incremental cost-effectiveness ratio at the 6-month follow-up for preloading relative to control was £710 (95% CI –£13,674 to £23,205), but preloading was dominant at 12 months and in the long term, with an 80% probability that it is cost saving. Limitations: The open-label design could partially account for the mediation results. Outcome assessment could not be blinded but was biochemically verified. Conclusions: Use of nicotine-patch preloading for 4 weeks prior to attempting to stop smoking can increase the proportion of people who stop successfully, but its benefit is undermined because it reduces the use of varenicline after preloading. If this latter effect could be overcome, then nicotine preloading appears to improve health and reduce health-service costs in the long term. Future work should determine how to ensure that people using nicotine preloading opt to use varenicline as cessation medication. Trial registration: Current Controlled Trials ISRCTN33031001.NIHR Health Technology Assessment programm