Reversible and Irreversible Effects of Temperature on Amelogenesis of Hamster Tooth Germs In Vitro

Hamster first hamster molar tooth germs in early secretory stage of amelogenesis were cultured for one day in vitro at 6°C, 22°C, 37°C or 45°C in the presence of 3H-proline, 45Ca and 32P-orthophosphate. Other explants were cultured without these labels and after culture examined by histology. The highest temperature tested was lethal to the explants, decreased total dry weight and rapidly increased total uptake of the radio-labelled mineral ions, probably merely due to physicochemical modification of the existing preculture minerals. Optimal synthesis and secretion of amelogenins were measured at physiological temperature (37°C). Effects of exposure to both temperatures below the physiological value were virtually reversible when explants were grown at physiological temperature (37°C) for another day. However, amelogenin secretion during this recovery period did not reach values as high as those found for the first day in explants initially grown at physiological temperature during the first day. We concluded from the four temperatures examined that the optimal temperature for enamel matrix deposition in vitro was 37°C. At this temperature enamel biosynthesis and its secretion are high. Lowering the temperature slows down the metabolism without any apparent harmful effect. Normal development of the tooth explants in vitro resumes when the culture temperature is restored to physiological levels (37°C). For temporary storage of tooth germ explants prior to any reimplantation, we therefore recommend a temperature of 6°C

The Impact of Having a 15-min Break With and Without Consuming an Energy Drink on Prolonged Simulated Highway Driving

Purpose: To examine whether consuming an energy drink while having a break is effective in reducing the number of lapses of attention during prolonged highway driving. Methods: In a double-blind crossover study, N = 21 healthy volunteers performed a 4-h driving test in the STISIM driving simulator. After 2 h, a 15-min break was scheduled. During the break, participants consumed either 250 ml of energy drink (ED) (Red Bull) or a placebo drink (Red Bull without caffeine (80 mg), glucuronolactone, taurine and B-vitamins). Participants were instructed to drive 95 km/h with a steady lateral position. Primary outcome was the number (#) of lapses; i.e., short periods of inattention defined by a deviation from the chosen lateral position for > 100 cm for 8 s or more. Results: Having a break, without consuming energy drink, significantly reduced the number of lapses in the 3rd hour of driving (9.9 versus 7.4 lapses, p = 0.006). After placebo, the number of lapses in the 4th and 2nd hour were identical (9.9 and 9.9 lapses, p = 1.000). Consuming and energy drink during the break resulted in a significant reduction in lapses in the 3rd hour (4.3 versus 9.2, p = 0.012) and 4th hour of driving (6.2 versus 9.2 lapses, p = 0.041), when compared with the 2nd hour of driving. Conclusion: Consuming an energy drink while having a 15-min break significantly reduces the number of lapses during prolonged highway driving, and to a greater extent than having a break only

The transcriptomic response of two basidiomycete fungi to plant biomass is modulated by temperature to a different extent

Many fungi show a strong preference for specific habitats and growth conditions. Investigating the molecular mechanisms of fungal adaptation to varying environmental conditions is of great interest to biodiversity research and is important for many industrial applications. In this study, we compared the transcriptome profiles of two previously genome-sequenced white-rot wood-decay fungi, Trametes pubescens and Phlebia centrifuga, during their growth on two common plant biomass substrates (wheat straw and spruce) at two temperatures (15 °C and 25 °C). The results showed that both fungi partially tailored their molecular responses to different types of carbon sources, differentially expressing genes encoding polysaccharide degrading enzymes, transporters, proteases and monooxygenases. Notably, more lignin modification related AA2 genes and cellulose degradation related AA9 genes were differentially expressed in the tested conditions of T. pubescens than P. centrifuga. In addition, we detected more remarkable transcriptome changes to different growth temperature in P. centrifuga than in T. pubescens, which reflected their different ability to adapt to the temperature fluctuations. In P. centrifuga, differentially expressed genes (DEGs) related to temperature response mainly encode protein kinases, trehalose metabolism, carbon metabolic enzymes and glycoside hydrolases, while the main temperature-related DEGs identified in T. pubescens are only the carbon metabolic enzymes and glycoside hydrolases. Our study revealed both conserved and species-specific transcriptome changes during fungal adaptation to a changing environment, improving our understanding of the molecular mechanisms underlying fungal plant biomass conversion at varying temperatures

Brain tumour diagnostics using a DNA methylation-based classifier as a diagnostic support tool

Aims: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. Methods: About 502 CNS tumour samples were analysed using (850 k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. Results: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score ≥0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect, the MP result predicted the right diagnosis for three of these cases. In six cases, the suggested class was interpreted as ‘discrepant but noncontributory’. The remaining 33.7% of cases (169/502) had a calibrated score <0.9, including 7.8% (39/502) for which no class indication was given at all (calibrated score <0.3). Conclusions: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information

Characteristics associated with significantly worse quality of life in mycosis fungoides/Sezary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study

Background Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. Aim To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. Methods Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. Results The study population consisted of 237 patients [60 center dot 3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (beta = 8 center dot 61; P = 0 center dot 003) and alopecia (beta = 9 center dot 71, P = 0 center dot 02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2 center dot 14, 95% confidence interval (CI) 1 center dot 19-3 center dot 89] and emotions (OR 1 center dot 88, 95% CI 1 center dot 09-3 center dot 27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Conclusions HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients.Peer reviewe

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when “at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication.” The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist