Vitamin D receptor expression and acid sphingomyelinase activity in prefrontal region of a learning animal model.

Contextual fear conditioning (CFC) paradigm is routinely used to study fear-based learning in animals and it provides a useful model for understanding fear and anxiety in human. In the present study, such model was used following the previously established CFC protocol, and immunohistochemistry, enzymatic activity and western blotting analysis approaches were used to identify the expression of acid sphingomyelinase (aSMase) and vitamin D receptor (VDR) in prefrontal region brain of rat. Results revealed an increase of aSMase activity in conditioned rats, suggesting an apoptotic condition in such animals. In addition, an increase of density and organization of axonal neurofilaments and of VDR expression has been observed in brain of conditioned rats, supporting an induction of growth and organization of new neurons in prefrontal regions, whose contribution to various aspects of contextual fear learning is still largely unknown.

Emergency Medical Service Information System:the ARES 118 experience.

BACKGROUND: In this paper we describe ARES 118, the prehospital Emergency Medical Service of the Region Lazio, Italy, focusing on its data system used to populate a data warehouse and to create ad hoc reports. ARES 118 is a regional public mono-specialized health company, established in 2004, that manages the emergency care throughout the Region Lazio. METHODS: Being a peculiar company in its kind, and being the first experience of this kind in Italy, ARES 118 has begun to equip itself, in an autonomous way, with a corporate information system, starting from what already existed as data collection from the individual provincial operating Centers and then by activating a unique information system at a regional and company level by deploying a data warehouse. All operations were carried out using open source software. RESULTS: Currently, ARES 118 is equipped with a business information system that enables data collection with its storage, management and processing of the same in fairly and easy way. The system allows the production of specific reports and measures modulated on the user requests in order to highlight the different aspects of the activity. CONCLUSIONS: The production of ad hoc reports, with the possibility of developing specific indicators, allows the identification and analysis of critical areas/processes in order to implement any corrective actions and monitor the effectiveness of the sam.

Global cardiovascular risk, COVID-19 severity and post-COVID-19 syndrome: a clinical study.

OBJECTIVE: Post-COVID-19 is a syndrome defined by signs and symptoms present until 12 weeks after COVID-19, lasting for more than 8 weeks, not explained by an alternative diagnosis. The present study aimed to assess whether the cardiovascular risk (CVR) of patients with COVID-19 correlates with symptoms and changes in respiratory function parameters in post-COVID-19. The association between CVR and the severity of acute disease was also considered. PATIENTS AND METHODS: Between 21/04/21-01/09/21, we enrolled 1,782 consecutive patients with COVID-19. We divided these subjects into (i) 4 levels, based on the severity of COVID-19 (home care; hospitalized/no oxygen therapy; hospitalized/oxygen therapy; hospitalized/NIV-ICU), (ii) 2 levels, according to CVR calculated with the European Society of Cardiology SCORE tables (low-intermediate risk; high or very high risk). All subjects underwent a 3-month follow-up considering post-COVID-19 symptoms. RESULTS: In post-COVID-19 patients, high or very-high CVR was associated with (i) increased risk of hospitalization for COVID-19 (p<0.0001), (ii) higher prevalence of severe clinical manifestations and ICU admission (p<0.0001), (iii) development of post-COVID-19 (p<0.0001) and (iv) increased risk of a larger post-COVID-19 burden of disease. CONCLUSIONS: We found a statistically significant association between CVR, severity of COVID-19, and post-COVID-19 syndrome three months after the end of acute disease.

Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

BRCA1 and BRCA2 germline mutations in Uruguayan breast and breast-ovarian cancer families. Identification of novel mutations and unclassified variants.

The aim of the present study was to analyze BRCA1 and BRCA2 mutations in Uruguayan families with breast and breast/ovarian cancer. Probands from 42 families with at least three cases of female breast cancer (BC) or two cases and subcriteria (paternal transmission, ovarian cancer, bilateral BC, male BC, Ashkenazi Jewish ancestry) in the same lineage, at least one diagnosed before age 50, were screened for germline mutations. PCR amplification of all exons and intron-exon boundaries were performed, followed by protein truncation test, heteroduplex analysis, and direct sequencing. We identified seven different truncating mutations in seven families, five in BRCA2 (three in site-specific BC families and two in breast-ovarian cancer families) and two in BRCA1 (one in a site-specific BC family and the other in a breast-ovarian cancer family). Both BRCA1 mutations (5583insT and 2687T>G) and one of the five BRCA2 mutations (3829insTdel35) were not previously reported. We also detected ten sequence variants of unknown significance, five of them not described before. The low frequency of BRCA1/2 mutations (0.17) is in agreement with that reported in studies which included families with similar selection criteria. However, the observed predominance of BRCA2 (0.12) over BRCA1 mutations (0.05) is in contrast with the higher proportion of BRCA1 mutations communicated for most previous studies, even those with a predominance of site-specific BC families. Meanwhile, it has been described in one Chilean and some Spanish and Italian reports, highlighting the strong dependence between the mutational spectra and the ethnicity of the population analyzed.

[Malnutrition in the elderly: clinical features, psychological and social determinants. Preliminary results]. / La malnutrizione in età geriatrica: caratteristiche cliniche e determinanti psico-sociali (MEG). Risultati preliminari.

In industrialized Countries malnutrition is a very frequent condition in frail groups of the population, people with low income and elderly subjects above all if institutionalized. The aim of the study is to: analyse the prevalence of malnutrition in a sample of elderly people located in different geographical areas in Italy; identify the psychological, social, economic, environmental, cultural and demographic determinants of malnutrition. The prevalence of malnutrition (estimated through the MNA) is high in both sexes (28% of F and 21.9% of M. Age, institutionalisation, health status, autonomy status, cognitive status and education level are some of the factors that correlate with the presence of malnutrition. Loneliness and poverty seem to have a negative impact on nutritional status but further data are needed to confirm this hypothesis. The data collected confirm the need to activate services dedicated to assess the nutritional status of elderly people, to implement campaigns in particular on food education for the elderly population, to set tools and guide lines for caregivers.

The nuclear ceramide/diacylglycerol balance depends on the physiological state of thyroid cells and changes during UV-C radiation-induced apoptosis.

Intranuclear lipid metabolism modifications in relation to cell proliferation and/or apoptosis were demonstrated in hepatocytes. The aim of this study was to establish whether nuclear lipid metabolites influence cell function in different experimental models using a rat thyroid cell line (FRTL-5) treated with UV-C radiation. After UV-C irradiation cells proliferate and undergo apoptosis in the presence of thyrotropin, are quiescent and resistant to radiation-induced apoptosis in its absence and finally are proapoptotic for nutrition withdrawal. In nuclei purified from proliferating cells, irradiation stimulates neutral-sphingomyelinase activity and inhibits sphingomyelin-synthase, phosphatidylcholine-specific phospholipase C and phosphatidylinositol-specific phospholipase C activity with a consequent increase in the ceramide/diacylglycerol ratio. This effect is marked in proapoptotic cell nuclei and low in quiescent cell nuclei. In conclusion, UV-C radiation induces apoptosis, modifying nuclear lipid metabolism in relation to the physiological state of cells.

In Vitro Protective Effects of Lycium barbarum Berries Cultivated in Umbria (Italy) on Human Hepatocellular Carcinoma Cells.

Lycium barbarum is a famous plant in the traditional Chinese medicine. The plant is known to have health-promoting bioactive components. The properties of Lycium barbarum berries cultivated in Umbria (Italy) and their effect on human hepatocellular carcinoma cells (HepG2) have been investigated in this work. The obtained results demonstrated that the Lycium barbarum berries from Umbria region display high antioxidant properties evaluated by total phenolic content and ORAC method, on hydrophilic and lipophilic fractions. Moreover, on HepG2 cell line Lycium barbarum berries extract did not change cell viability analyzed by MTT and Trypan blue exclusion assay and did not induce genotoxic effect analyzed by comet assay. Furthermore, it was demonstrated, for the first time, that the berries extract showed a protective effect on DNA damage, expressed as antigenotoxic activity in vitro. Finally, Lycium barbarum berries extract was able to modulate the expression of genes involved in oxidative stress, proliferation, apoptosis, and cancer. In particular, downexpression of genes involved in tumor migration and invasion (CCL5), in increased risk of metastasis and antiapoptotic signal (DUSP1), and in carcinogenesis (GPx-3 and PTGS1), together with overexpression of tumor suppressor gene (MT3), suggested that Umbrian Lycium barbarum berries could play a protective role against hepatocellular carcinoma.

Intraoperative autologous blood transfusion in intracranial surgery.

OBJECTIVE: The purpose of this study was to evaluate the benefits of intraoperative autotransfusion of autologous blood on the conservation of allogenic blood, including cost-effectiveness and the consequences for hemoglobin level and coagulation tests. METHODS: The Hoemonetics Cell Saver 4 autotransfusion system (Hoemonetics Corporation, MA) was used when the estimated blood loss was equal to or more than 500 ml. A total of 472 patients undergoing intracranial surgery were included in the study. RESULTS: Ninety patients (19%) received transfusions either with autologous blood or allogenic blood. Fifty-five patients (61%) received only autologous blood transfusions, 10 patients (11%) received both autologous and allogenic blood transfusions, and 25 patients (28%) received only allogenic blood transfusions. The amount of autologous blood transfused was 600 +/- 590 ml (range, 230-3000 ml). The amount of allogenic blood transfused was 3 +/- 3 units (range, 2-15 units). Autologous blood represented 68% of all blood products transfused. Mild abnormalities during coagulation tests occurred without clinical bleeding. CONCLUSION: Autologous blood transfusions were demonstrated to be safe in patients undergoing intracranial surgery and to be more cost-effective than allogenic blood transfusions. Intraoperative autologous blood transfusions may be used alone in more than half of the patients requiring transfusions during intracranial surgery and decrease the amount of allogenic blood used. Improvements in the monitoring for the need of performing this technique, as well as preoperative blood donations, would decrease the amount of allogenic blood transfused.

[Surgical strategy in gastric cancer in aged patients]. / Strategia chirurgica del cancro gastrico nel paziente anziano.

The trend of the National mortality rate for gastric cancer in the general population and in the old people between 1955 and 1990 was studied. A decreased incidence of mortality in the general population whereas an increased mortality rate in elderly was found. Between 1990 and 1994, 17 patients over 70 years of age were operated on for gastric cancer. The influence of the ASA classification on postoperative complications was then evaluated registering a significant statistical difference between patients included in ASA III group and or > and major complications and mortality (P = 0.044). The surgical strategy in the management of elderly patients with gastric cancer is also discussed.

Reinterpretation of mouse thyroid changes under space conditions: the contribution of confinement to damage.

During space missions, astronauts work in a state of separation from their daily social environment and in physical confinement. It has been shown that confinement influences mood and brain cortical activity, but no data has been obtained with regard to its effect on the thyroid gland, the structure and function of which change during spaceflights. Here, we report the results of a study on the effects of confinement on mouse thyroid, which was implemented with the Mice Drawer System Facility maintained on the ground, a system used for spaceflight experiments. The results show that confinement changes the microscopic structure of the thyroid gland and that it exhibits symptoms similar to those that result from physiological and/or pathological hyperfunction. What is left unchanged, however, is the sphingomyelinase-thyrotropin receptor relationship, which is important for thyrotropin response with a consequential production of hormones that act on the metabolism of almost all tissues and reduces the production of calcitonin, a hormone involved in bone metabolism. During space missions, the overexpression of pleiotrophin, a widespread cytokine up-regulated after tissue injury that acts on bone remodeling, attenuates changes to the thyroid that are spaceflight-dependent; therefore we studied the thyroids of pleiotrophin-transgenic mice in the Mice Drawer System Facility. In confinement, pleiotrophin overexpression does not protect from the loss of calcitonin. The contribution of confinement to thyroid damage during spaceflights is discussed.

Malnutrition in elderly: social and economic determinants.

UNLABELLED: Malnutrition occurs frequently in the frailest groups of the population, especially in people who are on a low income and elderly subjects, overall if they are institutionalized. The aim of this study was to assess the prevalence of malnutrition in a sample of elderly people living in different settings and to identify the determinants of malnutrition. METHODS: A total of 718 subjects, 472 females (F) and 246 males (M), were recruited from nursing homes or were free living in three different regions in Italy. Nutritional status, depression, social, functional and cognitive status, were evaluated. RESULTS: According to the Mini Nutritional Assessment (MNA), a high prevalence of malnutrition was found out in both genders: 26% of F and 16.3% of M were classified as being malnourished (MNA<17); 40.9% of F and 35% of M were at risk of malnutrition (MNA 17-23,5). The prevalence of malnutrition was significantly higher in NH subjects in both sexes. Moreover, a relationship was shown between malnutrition and inability to shop, prepare and cook meals because of a low income, distance from markets or supermarkets as well as impossibility to drive the car or to use public transportation. This study confirms the necessity to routinely perform nutritional status evaluation in elderly subjects, to carry out training courses for health workers (doctors, nurses, psychologists, dietitians), to implement nutritional education of the geriatric population, to develop tools and guidelines for health workers and caregivers, to identify and reduce clinical, functional, social or economic risk factors for malnutrition.

Low rectal cancer--what is the choice?

In patients operated on for low rectal cancer, the functional results, disease recurrence, and survival have been evaluated with respect to the type of surgery performed. Particular attention was paid to analysis of the pathologic aspects, considered in our opinion, as risk factors for recurrence. The investigation was carried out on 131 patients, of whom 70 received anterior resection, 55 abdominoperineal resection, and 6 local treatment. Abdominoperineal resection was carried out in more advanced disease. Postoperative mortality was 2.1 percent after anterior resection and 0 after abdominoperineal resection or local treatment. Follow-up, carried out in 96 patients (44 anterior resections, 46 abdominoperineal resections, and 6 local treatments), ranged from 12 to 84 (mean, 33.3) months. Recurrence rate was 53.3 percent after abdominoperineal resection and 28.9 percent after anterior resection. Recurrence appears not be related to the treatment performed, but rather depend on certain aspects of the neoplasm such as diameter exceeding 5 cm, extraparietal infiltration, lymphangitis, and tumor indifferentiation. We observed anastomotic recurrence in 28.6 percent of patients with a margin of less than 2 cm. An intensive follow-up scheme enabled us to recognize this type of recurrence early and to reoperate with radical intent. One year after anterior resection functional results were encouraging. No severe incontinence was reported. Local treatment was performed in carefully selected patients (T1, N0) and no cases of mortality or recurrence were observed.