Ketogenic nutritional therapy (KeNuT)-a multi-step dietary model with meal replacements for the management of obesity and its related metabolic disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-diet therapies in endocrinology and metabolism.

PURPOSE: The ketogenic nutritional therapy (KeNuT) is an effective dietary treatment for patients with obesity and obesity-related comorbidities, including type 2 diabetes, dyslipidaemia, hypertension, coronary artery disease, and some type of cancers. However, to date an official document on the correct prescription of the ketogenic diet, validated by authoritative societies in nutrition or endocrine sciences, is missing. It is important to emphasize that the ketogenic nutritional therapy requires proper medical supervision for patient selection, due to the complex biochemical implications of ketosis and the need for a strict therapeutic compliance, and an experienced nutritionist for proper personalization of the whole nutritional protocol. METHODS: This practical guide provides an update of main clinical indications and contraindications of ketogenic nutritional therapy with meal replacements and its mechanisms of action. In addition, the various phases of the protocol involving meal replacements, its monitoring, clinical management and potential side effects, are also discussed. CONCLUSION: This practical guide will help the healthcare provider to acquire the necessary skills to provide a comprehensive care of patients with overweight, obesity and obesity-related diseases, using a multistep ketogenic dietary treatment, recognized by the Club of the Italian Society of Endocrinology (SIE)-Diet Therapies in Endocrinology and Metabolism.

Role of Mediterranean diet in endocrine diseases: a joint overview by the endocrinologist and the nutritionist.

PURPOSE: The purpose of this review is to examine the current evidence on the potential role of Mediterranean diet (MD) in the prevention and management of endocrine disorders and to highlight the importance of interdisciplinary collaboration between endocrinologists and nutritionists. METHODS: A literature search was conducted using PubMed and Google Scholar databases to identify relevant studies published in English. Studies were selected based on their relevance to the role of MD in the prevention and management of endocrine disorders. The search terms included "Mediterranean diet," "endocrine disorders," "thyroid disorders," "gonadal disorders," and "neuroendocrine tumors". RESULTS: The studies reviewed suggest that MD may have a beneficial effect in the prevention and management of various endocrine disorders, including thyroid disorders, gonadal disorders, and neuroendocrine tumors. MD has been associated with decreased risk of nodular thyroid disease and thyroid cancer, improved male and female reproductive health, and a potential role in the management of neuroendocrine tumors. MD's anti-inflammatory and antioxidant properties, as well as its high levels of phytochemicals, may play a role in its beneficial effects. CONCLUSION: Interdisciplinary collaboration between endocrinologists and nutritionists is essential for the optimal management of endocrine disorders, including the potential role of MD in their prevention and management. While further research is needed, the current evidence suggests that MD may have a protective effect against endocrine disorders, and its incorporation into dietary recommendations may be beneficial.

Models of radon exhalation from building structures: General and case-specific solutions.

Assessing the radon activity that exhales from building structures is crucial to identify the best strategies to prevent radon from entering a building or reducing its concentration in the inhabited spaces. The direct measurement is extremely difficult, so the common approach has consisted in developing models describing the radon migration and exhalation phenomena for building porous materials. However, due to the mathematical complexity of comprehensively modelling the radon transport phenomenon in buildings, simplified equations have been mostly adopted until now to assess the radon exhalation. A systematic analysis of the models applicable to radon transport has been carried out and it has resulted in four models differing in the migration mechanisms - only diffusive or diffusive and advective - and the presence of inner radon generation. The general solutions have been obtained for all the models. Moreover, three case-specific sets of boundary conditions have been formulated to account for all the actual scenarios occurring in buildings: both perimetral and partition walls and building structures in direct contact with soil or embankments. The corresponding case-specific solutions obtained serve as a key practical tool to improve the accuracy in assessing the contribution of building materials to indoor radon concentration according to the site-specific installation conditions in addition to the material inner properties.

Extreme reverse seasonal variations of indoor radon concentration and possible implications on some measurement protocols and remedial strategies.

Indoor radon levels in dwellings are typically higher in cold months than in warm ones. The indoor radon concentration might experience an inverse seasonal behaviour - i.e., radon levels much higher in summer than in winter - under specific circumstances. In the framework of a study on long-term variations of annual radon concentration carried out in some tens of dwellings in Rome and surrounding small towns, two dwellings with very high - up to extreme - reverse seasonal variations were accidently discovered. These dwellings were located in a volcanic area, and they are both south-oriented and located on the lower part of a hill. In one of them, radon concentration was monitored by a continuous radon monitor for two years to find out when the greatest rises in radon levels occur. The indoor radon concentration resulted to experience extremely rapid, i.e. very few hours, increases up to 20 000 Bq m-3 during the spring period (i.e., April, May, and June especially). After about ten years from the first observation, the indoor radon concentration of the same house was monitored again for about five years: radon concentration peaks previously observed were found to be unchanged in terms of absolute values, duration, rising time and occurrence period. These reverse seasonal variations may lead to significant underestimation of the actual annual average radon concentration in case of measurements lasting less than one year if performed during the cold season and especially when seasonal correction factors are used. Moreover, these results suggest adopting specific measurement protocol and remediation strategies in houses having some peculiar characteristics, mainly regarding orientation, position, and attachment to the ground.

Effects of very low-calorie ketogenic diet on hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in controlling stress responses in humans under physiological and pathological conditions; cortisol is the main hormone produced by the HPA axis. It is known that calorie restriction acts as a stressor and can lead to an increase in cortisol production. Renin-angiotensin-aldosterone system (RAAS) is a complex endocrine network regulating blood pressure and hydrosaline metabolism, whose final hormonal effector is aldosterone. RAAS activation is linked to cardiometabolic diseases, such as heart failure and obesity. Obesity has become a leading worldwide pandemic, associated with serious health outcomes. Calorie restriction represents a pivotal strategy to tackle obesity. On the other hand, it is well known that an increased activity of the HPA may favour visceral adipose tissue expansion, which may jeopardize a successful diet-induced weight loss. Very low-calorie ketogenic diet (VLCKD) is a normoprotein diet with a drastic reduction of the carbohydrate content and total calorie intake. Thanks to its sustained protein content, VLCKD is extremely effective to reduce adipose tissue while preserving lean body mass and resting metabolic rate. PURPOSE: The purpose of this narrative review is to gain more insights on the effects of VLCKD on the HPA axis and RAAS, in different phases of weight loss and in different clinical settings.

Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists.

Aldosterone exerts deleterious effects on the cardiovascular system and promotes adipose tissue expansion via mineralocorticoid receptor (MR) activation. We previously demonstrated that administration of steroidal mineralocorticoid receptor antagonists (MRA) in mice fed a moderate high-fat diet is able to reduce white adipose tissue (WAT) expansion, stimulate browning of WAT and activate interscapular brown adipose tissue (iBAT). Here, we aimed to compare the metabolic and adipose tissue-specific effects of the novel non-steroidal MRA finerenone (Fine) and spironolactone (Spiro) in a mouse model of very high-fat diet (HFD)-induced obesity. C57BL/6 J male mice were fed a 60% HFD containing or not Spiro or Fine for 12 weeks. WAT and iBAT morphology and adipose tissue gene expression analysis were assessed. After 12 weeks, both groups of mice showed similar weight gain compared to the HFD group. Histological and molecular analyses of WAT did not show significant differences among all experimental groups; differently, iBAT histological analysis revealed that Fine was able to increase recruitment of brown adipocytes in this depot, whereas mice treated with Spiro failed to elicit any iBAT response, as indicated by no changes in lipid droplets size and iBAT density, compared to HFD. Increased iBAT recruitment could explain, at least in part, the improved insulin resistance observed in mice treated with Fine, as shown by a significant reduction in homeostasis model assessment of insulin resistance (HOMA) index. These findings were confirmed by gene expression analysis of ucp-1, pgc1-α, and beta-3 adrenoreceptor (Adrb3) in iBAT, revealing significantly higher expression of these thermogenic genes in HFD + Fine group compared to HFD, whereas Spiro did not modify their expression. In summary, we demonstrated that, differently from Fine, Spiro did not induce iBAT recruitment. Our current study suggests that Fine, through its direct effects on iBAT, represents a promising pharmacologic tool to treat human metabolic diseases associated with adipose tissue dysfunctions.

Nonsteroidal mineralcorticoid receptor antagonists: Novel therapeutic implication in the management of patients with type 2 diabetes.

Growing evidencehas described a correlation between aldosterone, obesity, and insulin resistance, suggesting that adipocyte-related factors and mineralocorticoid receptor (MR) overactivation may alter aldosterone secretion, potentially leading to obesity and glucose intolerance. Preclinical studies showed that pharmacological antagonism of MR prevents white adipose tissue dysfunction(s) and expansion, activates brown adipose tissue, and improves glucose tolerance. The clinical use of nonsteroidal MR antagonists has been shown to reduce the risk of diabetic kidney disease progression and cardiovascular events in patients with diabetes. This review aims to summarize the effects of pharmacological MR blockade on obesity and its associated metabolic comorbidities, with a particular focus on the therapeutic implications of nonsteroidal MR antagonists in the management of patients with diabetes.

Impact of temporal variability of radon concentration in workplaces on the actual radon exposure during working hours.

For workplaces where significant diurnal variations in radon concentrations are likely, measurements to evaluate average radon concentration during working hours could be useful for planning an optimized protection of workers according to the 2013/59/Euratom Directive. However, very few studies on this subject, generally limited to periods of few weeks, have been published. Therefore, a study has been conducted to evaluate the actual long-term radon exposure during working hours for a sample of 33 workplaces of four different types (postal offices, shops, restaurants, municipal offices), mainly located at the ground floor, and with expected considerable air exchange rate occurring during working hours due to frequent entrance/exit of persons or mechanical ventilation. The results show that the difference between the average radon level during working hours and that one during the whole day is about 20% on average and ranges from 0 to 50%. These observed differences, generally smaller compared with those found in other similar studies, are nearly the same if the analysis is restricted to workplaces with annual radon level higher than 300 Bq m-3, and therefore natural or mechanical ventilation normally present during working hours of the monitored workplaces cannot be considered an effective mitigation measure. However, the costs and time-response characteristics of the active monitors, as those used for the present study, will probably allow using more frequently a similar measurement strategy in workplaces.

Quantifying the Contribution of Seed Blended Refugia in Field Corn to Helicoverpa zea (Lepidoptera: Noctuidae) Populations.

Helicoverpa zea (Boddie), a pest of cotton that also occurs in field corn, is commonly controlled through the use of foliar-applied insecticides or transgenic crops expressing Bacillus thuringiensis (Berliner) (Bt) genes. To minimize the risk of Bt resistance in pest populations, refuge systems have been implemented for sustainable agroecosystem management. Historically, structured refuge compliance among growers has been low, leading to the commercialization of seed blended refugia. To test the viability of seed blended refugia in southern U.S. field corn, field studies were conducted in Mississippi and Georgia during 2016, 2017, and 2018 growing seasons. To quantify adult H. zea emergence from structured (non-Bt corn) and seed blended refuge options, emergence traps were utilized. Kernel damage among seed blended refuge and structured refuge corn ears were recorded and compared. The timing of moth emergence was recorded. When compared to a structured refuge, H. zea adult moth emergence from seed blended refugia did not significantly differ. Kernel damage of non-Bt plants in the seed blended treatments was not significantly different than non-Bt plants in the structured refuge treatments. Moth emergence timing was not significantly delayed between the structured refuge and seed blended refuge treatments. Results of this study suggest that a seed blended refuge may provide an effective insecticide resistance management alternative for H. zea in areas where structured refuge compliance is low.

SHORT-TERM ANNUAL VARIATIONS OF RADON CONCENTRATION IN WORKPLACES: SOME RESULTS IN A RESEARCH INSTITUTE.

Many international and national regulations on radon in workplaces, including the 2013/59/Euratom Council Directive, are based on the annual average of indoor radon concentration, assuming it is representative of the long-term average. However, a single annual radon concentration measurement does not reflect annual variations (i.e. year-to-year variations) of radon concentration in the same location. These variations, if not negligible, should be considered for an optimized implementation of regulations. Unfortunately, studies on annual variations in workplaces can be difficult and time-consuming and no data have been published on scientific journals on this issue. Therefore, we carried out a study to obtain a first evaluation of short-term annual variations in workplaces of a research institute in Rome (Italy). The radon concentration was measured in 120 rooms (mainly offices and laboratories) located in 23 buildings. In each room, two 1-year long measurements were performed, with an interval between the two measurements of up to 3 years. The results show variability between the two 1-year long measurements higher than the variability observed in a sample of dwellings in the same area. Further studies are required to confirm the results and to extend the study to other types of workplaces.

REPRODUCIBILITY OF RADON-IN-WATER MEASUREMENTS BY EMANOMETRY TECHNIQUE.

The emanometry test method is one of the detection techniques of radon in water satisfying requirements of Directive 2013/51/Euratom with regards to the detection limit. Quality assurance (QA) procedures were developed and implemented for a measuring system relying on such a technique. These procedures mainly address the following: (i) the assembling of each component of the degassing circuit, (ii) the sample transfer from the transport container to the degassing vessel and (iii) the control of all the influencing quantities. Three identical measuring systems have been used to analyse in parallel 39 water samples with the aim to evaluate the effectiveness of QA procedures in terms of reproducibility. The results showed quite low variability (<15% for the 84% of measurements in the range 10-100 Bq L-1) among the three different measuring systems.

SPATIAL VARIABILITY OF INDOOR RADON CONCENTRATION IN SCHOOLS: IMPLICATIONS ON RADON MEASUREMENT PROTOCOLS.

The requirements about radon measurements in schools and public buildings included in most of the national and international legislations are generally restricted to all the rooms located at the ground floor and basement, assuming the soil beneath the building as the main source of indoor radon. In order to verify such an assumption for small buildings having at maximum two floors, a preliminary study was performed in 50 schools located in 15 municipalities of the Republic of Srpska. Results of this study suggest that a protocol requiring measurements at the ground floor only may be considered adequate. Due to the high radon spatial variability for rooms at the ground floor, it is preferable to require measurements in a high number of rooms (preferably in all of them) in order to assess the compliance with the reference level established by the legislation.

EVALUATION OF REPRESENTATIVENESS OF SAMPLES USED FOR INDOOR RADON SURVEYS.

The estimation of the indoor radon exposure of the population of a country is generally carried out by the means of surveys designed in order to have sample representativeness as a target (population-based survey). However, the estimates of radon concentration distributions could be affected by biases if sampling was not random or in case of differences between sample and target population characteristics. In this work, we performed a preliminary check of the representativeness of the sample used for the second Italian national survey aimed to evaluate radon concentration distribution in each Province. We found that sampled dwellings are mostly located in the main administrative centres, where average radon concentration is generally lower, as compared with the other towns of the Province. The potential source of bias identified in this work suggests to carefully control the occurrence of a sampling imbalance between 'main' cities and other cities of Province and to take it into account in data analysis.

The value of routine laboratory screening in the neonatal intensive care unit.

BACKGROUND: Healthcare spending is expected to grow faster than the economy over the next decade, and the cost of prematurity increases annually. The aim of this study was to investigate the frequency of intervention after routine laboratory testing in preterm infants. METHODS: This was a retrospective study of preterm infants (≤34 weeks) admitted to the NYU Langone Health NICU from June 2013 to December 2014. Data collected included demographics, results of laboratory tests, and resulting interventions. Intervention after a hemogram was defined as a blood transfusion. Intervention after a hepatic panel was defined as initiation or termination of ursodiol or change in dose of vitamin D. Subjects were stratified into 3 groups based on gestation (<28 weeks, 28-31 6/7 weeks, 32-34 weeks). Chi-square analysis was used to compare the frequency of intervention between the groups. RESULTS: A total of 135 subjects were included in the study. The frequency of intervention after a hemogram was 8.4% in infants <28 weeks, 4.6% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks; this difference was found to be statistically significant (p = 0.02). The frequency of intervention after a hepatic panel was 4.2% in infants <28 weeks, 5.7% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks, which was not found to be a statistically significant different. CONCLUSION: No interventions were undertaken post-routine laboratory testing in any infant 32-34 weeks and routine testing in this population may be unnecessary. Further studies are needed to elucidate if routine testing affects neonatal outcomes.

Analysis of the Trend Over Time of High-Urgency Liver Transplantation Requests in Italy in the 4-Year Period 2014-2017.

BACKGROUND: The national protocol for the handling of high-urgency (HU) liver organ procurement for transplant is administered by the Italian National Transplant Center. In recent years, we have witnessed a change in requests to access the program. We have therefore evaluated their temporal trend, the need to change the access criteria, the percentage of transplants performed, the time of request satisfaction, and the follow-up. METHODS: We analyzed all the liver requests for the HU program received during the 4-year period of 2014 to 2017 for adult recipients (≥18 years of age): all the variables linked to the recipient or to the donor and the organ transplants are registered in the Informative Transplant System as established by the law 91/99. In addition, intention to treat (ITT) survival rates were compared among 4 different groups: (1) patients on standard waiting lists vs (2) patients on urgency waiting lists, and (3) patients with a history of transplant in urgency vs (4) patients with a history of transplant not in urgency. RESULTS: Out of the 370 requests included in the study, 291 (78.7%) were satisfied with liver transplantation. Seventy-nine requests (21.3%) have not been processed, but if we consider only the real failures, this percentage falls to 13.1% and the percentage of satisfied requests rises to 86.9%. The average waiting period for liver transplantation (LT) is 1.7 days and most requests (74%) are met in less than 24 hours, if we consider the hours between the registration of the request and the donor reporting . The percentage of late retransplantations is 2.1%. The clinical indication for HU-LT that appears to improve over time is hepatic artery thrombosis (82.5%). The overall 1-year patient survival is 68.3%. The overall 1-year graft survival, performed on all the patients, is 89% and all the indications for HU-LT appear to go well over time with an average survival rate greater than 85%. CONCLUSIONS: The indications for HU-LT are changing according to the changes in the hepatologic field in recent years. The centralized management of requests has proven to be successful in optimizing responses. Urgent LT is confirmed to be lifesaving in its timeliness.

Sarcopenic obesity: etiology and lifestyle therapy.

OBJECTIVE: Sarcopenic obesity (OS) is a multifactorial condition characterized by the simultaneous presences of sarcopenia and obesity. The prevalence of OS is increasing in adults over 65 years of age; people with OS present greater health risks than people who are only sarcopenic or obese. Therefore, the study of OS and the search for effective treatment are important due to the constant increase of the elderly population. MATERIALS AND METHODS: This review discusses the etiology and evolutionary mechanisms of OS while exploring its molecular, metabolic, oxidative, inflammatory, hormonal, and nutritional stresses. Studies have tried to unravel the causes related to the onset of sarcopenia, which is responsible for the decrease of muscle mass and strength in elderly subjects. The diagnostic criteria and the methods of evaluation of OS are described in these research studies, although there is no univocal definition for these parameters. The most studied treatments in OS are illustrated and highlight how the physical activity performed through both aerobic and resistance exercises, as well as a correct nutritional treatment, prove to be the most effective interventions in the regression of the pathology and in the improvement of physical function. RESULTS: New therapies for OS are hypothesized that will open the way to other possible types of intervention in the future. CONCLUSIONS: The deficiency of muscle mass in obese elderly subjects will be one of the health challenges of the future to reduce the risk of chronic diseases.

Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

Use of ultrasound shear wave to measure muscle stiffness in children with cerebral palsy.

PURPOSE: Cerebral palsy (CP) is a disorder characterized by an increased muscle stiffness that can be contingent on both neurological and biomechanical factors. The neurological aspects are related to hyper-excitability of the stretch reflex, while the biomechanical factors are related to modifications in muscle structure. We used smart-shear wave elastography (S-SWE) to analyze muscle properties and to compare shear wave speed in soleus muscles of patients affected by CP and typically developing children. METHODS: We enrolled 21 children (15 males and 6 females; age range 3-16) with spastic hemiplegia CP and 21 healthy children (11 males and 10 females; age range 3-14). Measurements of soleus S-SWE were performed using a Samsung RS80A ultrasound scanner with Prestige equipment (Samsung Medison Co. Ltd., Seoul, Korea), with a convex array transducer (CA1-7; Samsung Medison Co. Ltd., Seoul, Korea). For each CP child clinical assessment included Modified Ashworth Scale (MAS) score. RESULTS: Children with CP showed greater S-SWE values than the healthy ones (p < 0.001). Our data suggest a significant correlation between the S-SWE values and the MAS scores (Spearman correlation coefficient 0.74; p < 0.001 at Kruskal-Wallis test) in children with CP. CONCLUSIONS: Measuring muscle properties with SWE, a non-invasive and real-time technique, may integrate the physical exam. SWE may be a reliable clinical tool for diagnosis and longitudinal monitoring of muscle stiffness, as well as particularly suitable for grading and for assessing the response to treatments.