Diet and Physical Activity in Adult Dominant Polycystic Kidney Disease: A Review of the Literature.

Autosomal polycystic kidney disease is the most common inherited kidney disease determining 5% of all end-stage kidney disease. The only therapy approved for this condition is Tolvaptan, which, with its aquaretic effect, has a strong effect on patients' daily life. Recently, the literature has been enriched with new works that analyze possible non-pharmacological therapeutic strategies to slow cysts' enlargement and chronic kidney disease progression. Among them, dietary schemes reducing carbohydrate intake and inducing ketoses have been demonstrated to have efficacy in several pre-clinical and clinical studies. A ketogenic diet, calorie restriction, intermittent fasting, and time-restricted feeding can reduce aerobic glycolysis and inhibit the mTOR pathway, producing a reduction in cyst cell proliferation, a reduction in kidney volume, and helping to preserve kidney function. ADPKD's burden of disease has an impact on patients' quality of life, and the possibility to play sports or carry out physical exercise can help people in everyday life. The multisystemic character of the disease, especially cardiovascular involvement, needs to be carefully evaluated to establish the quality and quantity of physical activity that patients can safely carry out.

Using oxygen dose histograms to quantify voxelised ultra-high dose rate (FLASH) effects in multiple radiation modalities.

Purpose.To introduce a methodology to predict tissue sparing effects in pulsed ultra-high dose rate radiation exposures which could be included in a dose-effect prediction system or treatment planning system and to illustrate it by using three published experiments.Methods and materials.The proposed system formalises the variability of oxygen levels as an oxygen dose histogram (ODH), which provides an instantaneous oxygen level at a delivered dose. The histogram concept alleviates the need for a mechanistic approach. At each given oxygen level the oxygen fixation concept is used to calculate the change in DNA-damage induction compared to the fully hypoxic case. Using the ODH concept it is possible to estimate the effect even in the case of multiple pulses, partial oxygen depletion, and spatial oxygen depletion. The system is illustrated by applying it to the seminal results by Town (Nat. 1967) on cell cultures and the pre-clinical experiment on cognitive effects by Montay-Gruelet al(2017Radiother. Oncol.124365-9).Results.The proposed system predicts that a possible FLASH-effect depends on the initial oxygenation level in tissue, the total dose delivered, pulse length and pulse repetition rate. The magnitude of the FLASH-effect is the result of a redundant system, in that it will have the same specific value for a different combination of these dependencies. The cell culture data are well represented, while a correlation between the pre-clinical experiments and the calculated values is highly significant (p < 0.01).Conclusions. A system based only on oxygen related effects is able to quantify most of the effects currently observed in FLASH-radiation.

Incorporating oxygenation levels in analytical DNA-damage models-quantifying the oxygen fixation mechanism.

Purpose.To develop a framework to include oxygenation effects in radiation therapy treatment planning which is valid for all modalities, energy spectra and oxygen levels. The framework is based on predicting the difference in DNA-damage resulting from ionising radiation at variable oxygenation levels.Methods.Oxygen fixation is treated as a statistical process in a simplified model of complex and simple damage. We show that a linear transformation of the microscopic oxygen fixation process allows to extend this to all energies and modalities, resulting in a relatively simple rational polynomial expression. The model is expanded such that it can be applied for polyenergetic beams. The methodology is validated using Microdosimetric Monte Carlo Damage Simulation code (MCDS). This serves as a bootstrap to determine relevant parameters in the analytical expression, as MCDS is shown to be extensively verified with published empirical data. Double-strand break induction as calculated by this methodology is compared to published proton experiments. Finally, an example is worked out where the oxygen enhancement ratio (OER) is calculated at different positions in a clinically relevant spread out Bragg peak (SOBP) dose deposition in water. This dose deposition is obtained using a general Monte Carlo code (FLUKA) to determine dose deposition and locate fluence spectra.Results.For all modalities (electrons, protons), the damage categorised as complex could be parameterised to within 0.3% of the value calculated using microdosimetric Monte Carlo. The proton beam implementation showed some variation in OERs which differed slightly depending on where the assessment was made; before the SOBP, mid-SOBP or at the distal edge. Environment oxygenation was seen to be the more important variable.Conclusions.An analytic expression calculating complex damage depending on modality, energy spectrum, and oxygenation levels was shown to be effective and can be readily incorporated in treatment planning software, to take into account the impact of variable oxygenation, forming a first step to an optimised treatment based on biological factors.

Pregnancy outcomes in substance-misusing pregnant women: A 10-year retrospective study.

In this ten-year retrospective study we were able to show that Maltese substance-misusing mothers (SMMs) have significantly different socio-biological characteristics from mothers in the general population which seem to impact on neonatal outcomes. Significant differences from the general population were noted in the SMM's age, age at first pregnancy, marital status, educational background, number of cigarettes smoked, number of offspring and weight gained in pregnancy. SMMs booked their pregnancy in hospital later than the general population. On the other hand their infants had a lower mean birth weight and head circumference, had lower Apgar scores, were of lesser gestational age and premature. They were less breast-fed and stayed longer in hospital after their birth.