Search

The well-known experiment of the rapid expansion and cooling of the air contained in a bottle is performed with a rapidly responsive, yet very cheap thermometer. The adiabatic, low temperature limit is approached quite closely and measured with our apparatus. A straightforward theoretical model for this process is also presented and discussed. Both the experimental setup and the associated theoretical interpretation of the cooling phenomenon are suited for a standard general physics course at undergraduate level. (Contains 6 figures.)

A simple experiment is presented to visualize inferior and superior mirages in the laboratory. A quantitative analysis is done using ray tracing with both photographic and computational techniques. The mirage's image, as seen by the eye or the camera lens, can be used to analyse the deflection and inversion of light rays. (Contains 6 footnotes, 1 table and 10 figures.)

We discuss some simple experiments dealing with intriguing properties of light and its interaction with matter. In particular, we show how to emphasize that light reflection, refraction and scattering can provide a proper, physical description of human perception of the "colour" white. These experiments can be used in the classroom with an enquiry approach, and it is in this spirit that we will present them. (Contains 3 footnotes and 4 figures.)

We discuss three methods of measuring the density of air most commonly used in a teaching context. Emphasis is put on the advantages and/or difficulties of each method. In particular, we show that the 'rubber balloon' method can still be performed with meaningful physical insight, but it requires a very careful approach. (Contains 4 figures and 3 tables.)

As is well known, scientific entertainment can be a fruitful way to attract people of any age to science. Depending on the specific purpose, different mixtures of science and amusement can be considered, so emphasizing scientific education with respect to fun aspects or vice versa. Moreover, when proposing "hands-on" activities in such learning contexts, group participation and the development of manual skills are often achieved. Science centres and museums play an important role in this respect. Informal learning is a widely recognized and constantly developing approach to the familiarization of scientific subjects to a large, occasional audience. In this article, the authors propose a new format of scientific entertainment in which customers of a restaurant can order small experiments in place of entrees and drinks. (Contains 3 figures.)

The glutathione (GSH) system is the main defence of tissues against free radicals and red blood cells (RBC) are the most efficient sites for GSH redox cycle activation. Total GSH was assayed during cardiopulmonary bypass (CPB) in RBC and serum from the coronary sinus, peripheral arteries and veins in 18 children corrected of their cardiac defect. Our conclusions are: (l) RBC-GSH redox cycle is activated during heart ischaemia and reperfusion; (2) the activation of intracellular GSH system is preponderant compared with the extracellular one; (3) variations in intraerythrocytic total GSH during heart ischaemia and perfusion are detectable in peripheral veins and arteries, which can be the convenient sites for monitoring changes in the GSH cycle; and (4) increased total GSH levels are present in RBC before aortic crossclamping: at the beginning of mechanical ventilation in veins and, when CPB is started, also in arteries. [ABSTRACT FROM AUTHOR]

The glutathione (GSH) system is the main defence of tissues against free radicals and red blood cells (RBC) are the most efficient sites for GSH redox cycle activation.Total GSH was assayed during cardiopulmonary bypass (CPB) in RBC and serum from the coronary sinus, peripheral arteries and veins in 18 children corrected of their cardiac defect. Our conclusions are: (1) RBC-GSH redox cycle is activated during heart ischaemia and reperfusion; (2) the activation of intracellular GSH system is preponderant compared with the extracellular one; (3) variations in intraerythrocytic total GSH during heart ischaemia and perfusion are detectable in peripheral veins and arteries, which can be the convenient sites for monitoring changes in the GSH cycle; and (4) increased total GSH levels are present in RBC before aortic crossclamping: at the beginning of mechanical ventilation in veins and, when CPB is started, also in arteries. [ABSTRACT FROM PUBLISHER]

Findings of early cerebral amyloid-β deposition in mice after peripheral injection of amyloid-β-containing brain extracts, and in humans following cadaveric human growth hormone treatment raised concerns that amyloid-β aggregates and possibly Alzheimer's disease may be transmissible between individuals. Yet, proof that Aβ actually reaches the brain from the peripheral injection site is lacking. Here, we use a proteomic approach combining stable isotope labeling of mammals and targeted mass spectrometry. Specifically, we generate 13 C-isotope-labeled brain extracts from mice expressing human amyloid-β and track 13 C-lysine-labeled amyloid-β after intraperitoneal administration into young amyloid precursor protein-transgenic mice. We detect injected amyloid-β in the liver and lymphoid tissues for up to 100 days. In contrast, injected 13 C-lysine-labeled amyloid-β is not detectable in the brain whereas the mice incorporate 13 C-lysine from the donor brain extracts into endogenous amyloid-β. Using a highly sensitive and specific proteomic approach, we demonstrate that amyloid-β does not reach the brain from the periphery. Our study argues against potential transmissibility of Alzheimer's disease while opening new avenues to uncover mechanisms of pathophysiological protein deposition., (© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

CLN5 disease is a rare form of late-infantile neuronal ceroid lipofuscinosis (NCL) caused by mutations in the CLN5 gene that encodes a protein whose primary function and physiological roles remains unresolved. Emerging lines of evidence point to mitochondrial dysfunction in the onset and progression of several forms of NCL, offering new insights into putative biomarkers and shared biological processes. In this work, we employed cellular and murine models of the disease, in an effort to clarify disease pathways associated with CLN5 depletion. A mitochondria-focused quantitative proteomics approach followed by functional validations using cell biology and immunofluorescence assays revealed an impairment of mitochondrial functions in different CLN5 KO cell models and in Cln5 - /- cerebral cortex, which well correlated with disease progression. A visible impairment of autophagy machinery coupled with alterations of key parameters of mitophagy activation process functionally linked CLN5 protein to the process of neuronal injury. The functional link between impaired cellular respiration and activation of mitophagy pathways in the human CLN5 disease condition was corroborated by translating organelle-specific proteome findings to CLN5 patients' fibroblasts. Our study highlights the involvement of CLN5 in activation of mitophagy and mitochondrial homeostasis offering new insights into alternative strategies towards the CLN5 disease treatment., Competing Interests: Conflict of interestAlessandro Simonati received honoraria for consultancy from Bio-Marin Pharmaceutical, Inc and Neurogene Co; the remaining authors declare that they have no conflict of interest., (© The Author(s) 2020.)

The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2.586 differentially expressed gene loci (2.175 annotated genes). The analyses pinpointed the fructose-induced glycolysis-pathway to be markedly active in 1-day-old neonatal mice. Integrated analysis of the data convincingly demonstrated cardiac metabolic reprogramming from glycolysis to oxidative phosphorylation in 7-days old mice, with increases of key enzymes and metabolites in fatty acid transport (acylcarnitines) and β-oxidation. An upsurge in the formation of reactive oxygen species and an increase in oxidative stress markers, e.g., lipid peroxidation, altered sphingolipid and plasmalogen metabolism were also evident in 7-days mice. In vitro maintenance of physiological fetal hypoxic conditions retained the proliferative capacity of cardiomyocytes isolated from newborn mice hearts. In summary, we provide here a holistic, multiomics view toward early postnatal changes associated with loss of a tissue regenerative capacity in the neonatal mouse heart. These results may provide insight into mechanisms of human cardiac diseases associated with tissue regenerative incapacity at the molecular level, and offer a prospect to discovery of novel therapeutic targets.

Metformin is the first line drug for type 2 diabetes but its molecular mechanisms remain unclear. Here, we have studied the acute effect of a therapeutically relevant intrahepatic concentration of metformin on glucose production from lactate. We selected the perfused rat liver as experimental system since it enables the complete control of drug dosage. We used MALDI (matrix-assisted laser desorption/ionization) mass spectrometry imaging to estimate the concentration of metformin in the livers and we measured the concentration of glucose in the effluent medium under basal conditions and following lactate addition. MALDI mass spectra of thin-sections of freeze-clamped rat liver perfused with metformin showed a peak at 130.16 m/z which was unambiguously assigned to metformin. The mass spectrometric detection limit was at a tissue concentration of about 250 nM, and uptake of metformin from the perfusion medium to the liver occurred with a K m of 0.44 mM. Metformin was evenly distributed in the liver irrespective of its concentration in the perfusion medium and the duration of a perfusion. At a parenchymal concentration of 30 μM, metformin did not induce any significant suppression of the basal or lactate-induced glucose release from the liver. These results show that matrix-assisted laser desorption/ionization mass spectrometry imaging can be applied to estimate the tissue concentration and distribution of metformin in a therapeutically relevant micromolar concentration range. Our findings challenge the view that metformin causes an inhibition of glucose release from the liver by an acute inhibition of mitochondrial glycerol 3-phosphate dehydrogenase (EC 1.1.5.3).

Introduction: Neurological disorders encompass various pathologies which disrupt normal brain physiology and function. Poor understanding of their underlying molecular mechanisms and their societal burden argues for the necessity of novel prevention strategies, early diagnostic techniques and alternative treatment options to reduce the scale of their expected increase. Areas covered: This review scrutinizes mass spectrometry based approaches used to investigate brain dynamics in various conditions, including neurodegenerative and neuropsychiatric disorders. Different proteomics workflows for isolation/enrichment of specific cell populations or brain regions, sample processing; mass spectrometry technologies, for differential proteome quantitation, analysis of post-translational modifications and imaging approaches in the brain are critically deliberated. Future directions, including analysis of cellular sub-compartments, targeted MS platforms (selected/parallel reaction monitoring) and use of mass cytometry are also discussed. Expert commentary: Here, we summarize and evaluate current mass spectrometry based approaches for determining brain dynamics in health and diseases states, with a focus on neurological disorders. Furthermore, we provide insight on current trends and new MS technologies with potential to improve this analysis.

Background: To evaluate oxidative stress and myocardial damage after aortic crossclamping release (ACCR) during cardio pulmonary bypass (CPB) in children two parameters were investigated: total glutathione (GSH) and its oxidoreductive reactions (GSH/GSSG) as expression of oxidative stress, and plasmatic turnover of myocardial taurine (TAU) as expression of cell damage., Methods: The study was divided in two periods: 1) first period: analysis of oxidative stress and myocardial damage in 18 children. 2) Second period: evaluation of myocardial cell protection by controlled anterograde low oxygen warm reperfusion (ALOWR) before declamping. Twenty-one children were divided in two groups: not receiving (Group 1, 9 patients) and receiving (Group 2, 12 patients) ALOWR., Results: In the first period GSH values increased significantly after onset of mechanical ventilation (MV) in vein, after CPB start in artery and after ACCR in coronary sinus. Moreover TAU turnover in aortic and coronary sinus blood increased significantly after ACCR. In the second period, Group 2 showed a lower oxidative stress after ACCR, while no differences were observed in TAU turnover., Conclusions: 1) Assessment of TAU and GSH levels can be considered a good method to clinically evaluate myocardial injury during cardiac surgery. 2) MV and CPB can induce oxidative stress before aortic clamping and can decrease the physiologic scavengers. Therefore, to prevent that depletion, the strategy of these techniques must be adapted to the patient and to his cardiac disease. 3) Intramyocardial TAU turnover is not significantly modified by the reperfusion technique. 4) ALOWR can reduce myocardial oxidative stress and can improve heart recovery after the cardioplegic arrest.

Background: Complications of surgery of the descending thoracic aorta could include neurological problems such as paraparesis and paraplegia. Intestinal ischemia and acute renal failure could occur, too. During the cross-clamping time, the perfusion of the distal aorta by means of extracorporeal circulatory assistance can be useful to protect the spinal cord and the splanchnic organs and to reduce the incidence of these untoward events. The aim of this study was to verify the efficacy and suitability of this type of circulatory assistance in a pediatric age group., Methods: From January 1996 to March 2000, in the Pediatric Cardiac Surgery Department of the Gaslini Institute (Genoa, Italy), 6 patients (mean age 39 months, mean weight 14.4 kg) were treated using extracorporeal circulatory assistance through the left thoracotomy. Indications for surgery included the removal of a migrated device previously inserted in order to close a patent ductus arteriosus in 1 patient, recurrent coarctation in 2 patients, and native coarctation with a poor collateral circulation in 3 patients., Results: The early and late mortality rates as well as the morbidity rates (both neurological and splanchnic) were nil., Conclusions: Extracorporeal circulatory assistance can be helpful in pediatric patients and it can prevent neurological and renal injuries in cases of a) coarctation of the aorta with a poor collateral circulation and low distal pressure (< 40 mmHg during aortic occlusion); b) recoarctation with complex anatomy; c) other pathologies requiring prolonged descending thoracic aorta cross-clamping.

In the present study we try to analyze indications, contra-indication, side effects and limits of the use of extracorporeal circulation in neonatal and pediatric patients affected by reversible acute cardiorespiratory failure. The greatest experience on this technique has been achieved in the neonatal age (about 6000 newborns have been treated until now), while the employment in the pediatric age appears more recent (about 500 patients). Moreover, we focused on the drop-in criteria for neonatal and pediatric patients and on the clinical aspects and laboratory findings which can anticipate the surviving rate; the latter appears in any case much greater in the neonatal patient compared to the other pediatric ages.

From 1979 to 1990, 56 children ranging between 4 days and 16 years of age (mean 73 +/- 51 months) underwent Goretex patch aortoplasty for coarctation of the aorta. The mean weight at operation was 20.2 +/- 3.5 kg (range 3.3-42 kg). Forty-two patients had primary repair, and the remaining 14 had reoperation for recoarctation. The aorta was opened through a standard left thoracotomy, the posterior fibrous ridge was partially excised when it was prominent, and a large patch from a Goretex tube was sutured into place. The postoperative complications were as follows: paradoxical hypertension in 14 cases, massive haemorrhage due to aortic wall rupture in a diabetic child, and intestinal bleeding in 1 case. There were no early deaths and only 1 case of late death, which was not related to coarctation repair (mortality rate 1.8%). The average follow-up was 48 +/- 26 months. Continuous wave-Doppler examination at rest showed no arm-leg systolic gradient in 52 cases and a gradient of about 15 mmHg in 4 cases. Graded exercise testing showed only 1 case with an arm-leg gradient higher than 35 mmHg. Nuclear magnetic resonance (NMR) imaging, performed on 26 patients at a mean of 7 years from operation, showed excellent morphology and size of the aortoplasty. No cases of recoarctation or late aneurysm formation were found. We conclude that Goretex patch aortoplasty can be performed effectively and safely in children. Nuclear magnetic resonance provides high resolution imaging of the coarctation repair site.

An assessment was made of the efficacy of a beta-galactosidase, obtained from Aspergillus niger and added to intact milk, in decreasing lactose malabsorption and intolerance. Sixteen adult patients with malabsorption and intolerance to this sugar were studied in a double-blind crossover study vs. placebo. A 5-hour hydrogen breath test was used to assess malabsorption of lactose contained in 400 ml milk. When compared with placebo, the addition of exogenous lactase to intact milk caused a statistically significant reduction in the maximum breath H2 concentration (P less than 0.01) and in the cumulative H2 excretion (P less than 0.005). In the same way, the cumulative index for gastrointestinal intolerance was significantly lower (P less than 0.005) after the ingestion of lactase-added milk. This study demonstrates that enzyme replacement therapy, with beta-galactosidases obtained from Aspergillus niger, is effective in decreasing lactose malabsorption and its consequent intolerance in adult subjects with lactase deficiency.

Isolated primary fibrinolysis following cardiopulmonary bypass was fully prevented by using a modern washing technique for the reusable metal parts of the extracorporeal circuit: immersion in 20% caustic soda for 4 hr and in a detergent solution for a further 4 hr prior to rinsing and sterilisation. Reduction of bleeding from 558 to 465 cc/m2 was attributable an improved perfusion technique, early diagnosis and radical cleaning of the circuit. The disappearance of fibrinolysis, however, was entirely brought about by more thorough cleansing of the reusable metal parts.

The postoperative results in 150 patients who had repair of tetralogy of Fallot (mean follow-up, 10.2 +/- 2.6 years) were defined as good in 71.3%, fair in 20.7%, and unsatisfactory in 8.0% on the basis of clinical criteria. Ninety-six percent of the patients are socially active, 92.0% have a good exercise tolerance, and 79.3% participate in sports. Data from 78 postoperative hemodynamic studies show mild right ventricular dysfunction in almost all patients examined. Peak systolic right ventricular/left ventricular pressure ratio decreased in the postoperative period in 65.4% of patients, remained unchanged in 3.8%, and increased in 30.8%. Minimal residual anomalies can modify the prognosis substantially. Of our patients, 53.3% of those with a shunt (p less than 0.05), 37.5% of those with stenosis (not significant), and 53.8% of those with pulmonary incompetences (p = not significant) have fair or unsatisfactory results. The associated defects are particularly unfavorable. Rhythm and conduction disturbances have resulted in fair or unsatisfactory results in 65.1% of patients. Such a disturbance occurring soon after bypass must be considered an incremental risk factor: 52.9% of patients seen with rhythm and conduction disturbances show the same disturbances later (p less than 0.001).

The incidence of nosocomial infections (NI) and the related risk factors in a Department of Pediatric Cardiovascular Surgery were studied, during a 6 months period. 155 successive admissions were considered. Nosocomial infections were 17 (11%), nosocomial colonizations 18 (11.6%). The most important risk factors for nosocomial infections were: age, cyanosis, duration of hospitalization, hospitalization in Intensive Care Unit and central venous catheter only as a risk factor for sepsis. The most important risk factors for nosocomial colonizations were: tracheal intubation and central venous catheter. In 4 cases the NI was related to nosocomial colonization (2 sepsis, 1 pneumonia, 1 wound infection). The most frequently isolated microorganisms were Pseudomonas aeruginosa and Staphylococcus spp. The Authors found that a longer than 5 days period of antibiotic prophylaxis did not reduce the incidence of nosocomial infections.