Role of the femoral vein doppler in acute heart failure patients: results from a prospective multicentric study.

BACKGROUND AND OBJECTIVE: The aim of our study is to define the role of Pulsed-Doppler (PW-Doppler) Ultrasound of the Common Femoral Vein (CFV) in the assessment of dilatation Inferior Vena Cava (IVC), probability of Pulmonary Hypertension (PH), Tricuspid Regurgitation (TR), and Tricuspid annular plane systolic excursion (TAPSE). METHODS: This is a prospective two-hospital study in 74 patients admitted with acute heart failure (AHF). We performed PW-Doppler ultrasound of the common femoral vein, Point of Care (POC) cardiac ultrasonography and assessment of the IVC at the time of admission, as well as PW-Doppler and ultrasound of the IVC at hospital discharge. RESULTS: The detection of a pulsatile flow (138 scans) had an excellent ROC curve for the detection of IVC greater than 2cm (AUC 0.931, Sn 95%, Sp 90%, PPV 93%, NPV 94%) with an Odds Ratio (OR) of 211.2 (95% confidence interval 48.13-926.72). The pulsatility of the flow also had the highest performance in the detection of PH (AUC 0.8, Sn 95%, Sp 64%, PPV 84%, NPV 84%) and in the detection of moderate-severe TR (AUC 0.79, Sn 95%, Sp 67%, PPV 88%, NPV 78%). If the flow is continuous, we can reasonably rule out diminished TAPSE (NPV 89%). CONCLUSSION: Detection of PW-Doppler flow of the CFV may be an alternative window for the detection of an IVC dilation of 2cm, significant TR, and the likelihood of high PH in acute heart failure. It also allows us to reasonably rule out dysfunction of the right ventricle in cases of normality in these patients.

Scientific response to the 2021 eruption of Nyiragongo based on the implementation of a participatory monitoring system.

The development of a resilient society is a major challenge for growing human population faced with abundant natural hazards. During and after the May 22, 2021 eruption of Nyiragongo, the local population was surprised and scared by the subsequent seismicity and associated surface fracturing, coupled with the alert of a possible new eruptive vent opening in Goma (Democratic Republic of Congo) and/or Gisenyi (Rwanda). The creation of a toll-free phone number enabled the population to record fractures and gas/thermal anomalies affecting the area. Such work was fundamental in enabling scientists and authorities to assess the associated risks. Crucially, gas data showed that the degassing through fractures did not represent direct transfer of magmatic volatiles but was more likely of superficial origin. Surprisingly, this participatory work revealed that the first fractures appeared several weeks before the eruption and their opening was not detected by the monitoring system. This firmly underlines the need for scientists to anchor citizen science in monitoring strategies.

Trust of Italian healthcare professionals in COVID-19 (anti-SARS-COV-2) vaccination.

ABSTRACT: Background. Vaccination is one of the most effective tools available to Public Health. Its potential usefulness is threatened by the rise of vaccine hesitancy among the general population, which has grown as much as to prompt the World Health Organization to express its concerns on the matter. The risk posed by vaccine hesitancy is even more concerning in the light of the efforts to curb the ongoing COVID-19 pandemic, which focus mainly on mass vaccination campaigns. This holds especially true when applied to healthcare professionals, among whom vaccine hesitancy can be particularly detrimental. For these reasons, our study focuses on potential determinants of vaccine hesitancy among healthcare professionals. Study design. The study is a cross-sectional study. Methods. Data were collected from January 1st to February 16th, by means of a self-administered online questionnaire in a cohort of Italian healthcare professionals. Results. Overall, 10,898 questionnaires were collected. Among the respondents, 1.1% expressed vaccine hesitancy. Hesitancy was less frequent in professionals involved in Primary Care and in the Clinical Scien-ces/Public Health group. Among clinicians, paediatricians, oncologists, and geriatrists showed especially accepting attitudes towards vaccination. Lower hesitancy rates were also registered among the respondents who already had received influenza vaccination and who never had any adverse effects following vaccination. Higher hesitancy rates were observed among individuals who had family members aged >65 years and with a history of severe adverse reactions to vaccination. Conclusion. Vaccine hesitancy rates were extremely low among participants in our study. Some medical specialties shown were particularly accepting towards vaccination. The potential predictors and protective factors pointed out by our analysis might allow more refined targets.

Feasibility of biodegradable based packaging used for red meat storage during shelf-life: A pilot study.

This study was designated to ascertain the effectiveness of polylactic acid (PLA) based packaging solution to store red fresh meat during its refrigerated shelf-life. Recently the attention in the packaging industry regarding the use of bioplastics has been shifting from compostable/biodegradable materials toward biobased materials. Steaks obtained from semimembranous muscle of Piemontese beef were packaged in PLA trays closed with a lid made of PLA film and for comparison purposed in a conventional reference package consisting of a amorphous polyethylene terephthalate/polyethylene (APET/PET) trays and wrapped in plastic film of polyvinyl chloride (PVC). The packaging under modified atmosphere MAP was carried out by using a gas mixture of 66% O2, 25% CO2 and 9%N2. By using PLA packaging combination it was possible to maintain an optimum red colour together with a reduced content of volatile compounds associated to off-flavours of meat samples particularly related to the oxidation phenomena.

In vivo assessment of an industrial waste product as a feed additive in dairy cows: Effects of larch (Larix decidua L.) sawdust on blood parameters and milk composition.

When larch (Larix spp.) is processed in the wood industry, the sawdust is currently disposed of as waste or used as combustible material, even though it is rich in biologically active compounds. In this study the effect of larch sawdust supplementation on blood parameters as well as milk composition was examined in healthy mid-lactating dairy cows. Twenty-four multiparous Italian Friesian dairy cows were assigned to groups receiving either 300 g/day/cow of larch sawdust or a control diet, and treatments were continued for a 20 day period. Milk parameters were unaffected by treatment. A lower plasma total protein concentration was observed and can be attributed to a decrease in globulin concentration. A lower plasma urea concentration was also detected in the larch group. Moreover, biomarkers of liver function were influenced by the treatment. Total bilirubin was lower in larch-treated animals, and cholesterol tended to be lower. In addition, an interaction between day and treatment was observed for very low density lipoprotein. The concentration of other parameters, including reactive oxygen metabolites, superoxide dismutase, glutathione peroxidase and nitrotyrosine, did not differ between treatments. The observed benefits, together with the good palatability, make larch sawdust a promising candidate for the development of beneficial feed supplements for livestock. Further studies will be useful, particularly to evaluate its efficacy in different health conditions.

Silymarin and lycopene administration in periparturient dairy cows: effects on milk production and oxidative status.

AIMS: To establish during late gestation and early lactation the effects of supplementing silymarin, a natural hepatoprotective substance, combined with a powerful antioxidant, lycopene, on milk production and on serum biomarkers of oxidative status. METHODS: Italian Friesian dairy cows were given individually a supplement containing a mixture of silymarin (7.77 g/day/cow) and lycopene (1.27 g/day/cow) (n=10) or no supplement (control; n=10). Treatment was administered from 7 days before the expected calving date to the first 14 days in milk. At 7 days before the expected calving date, at calving, and 7 days postpartum, body condition score (BCS) and concentrations in serum of reactive oxygen metabolites (ROM), total antioxidant capacity (OXY) and thiobarbituric acid reactive substances (TBARS) were evaluated. Bodyweight, milk production, and somatic cell count (SCC) were determined at 7, 14 and 21 days postpartum. RESULTS: The mean time of treatment prior to calving was 6.3 (min 4, max 11) days. Compared with control cows, treatment increased energy corrected milk yield (33.3 vs. 37.8 (SEM 1.10) kg/day; p=0.006) and milk fat yield (1.14 vs. 1.32 (SEM 0.06) kg/day; p=0.05) over the first 21 days of lactation. Treated cows had lower mean log10 SCC compared to control cows (4.9 vs. 5.24 (SEM 0.11) log10 cells/mL) and had lower overall concentration of TBARS (1.47 vs. 1.59 (SEM 0.016) nM/mL; p<0.001), but similar concentrations of ROM and OXY in serum. However there was a treatment by time interaction (p=0.09) for OXY, and at calving mean OXY was higher in treated cows compared with pre-calving values (p<0.001). CONCLUSIONS: Despite the acknowledged limitation of the study, i.e. the small number of animals, our results suggest that silymarin and lycopene, as health-beneficial feed supplements, may help dairy cows in metabolic adaptation during the first stages of lactation. CLINICAL RELEVANCE: During the peripartum period dairy cows suffer moderate-to-severe fatty liver and from an overproduction of free radicals. The supplementation of a mixture of silymarin and lycopene during these stressful days may be useful to mitigate these metabolic disorders with beneficial effects on the subsequent lactation.

Inorganic contaminants from diffuse pollution in shallow groundwater of the Campanian Plain (Southern Italy). Implications for geochemical survey.

The Campanian Plain (CP) shallow aquifer (Southern Italy) represents a natural laboratory to validate geochemical methods for differentiating diffuse anthropogenic pollution from natural water-rock interaction processes. The CP is an appropriate study area because of numerous potential anthropogenic pollution vectors including agriculture, animal husbandry, septic/drainage sewage systems, and industry. In order to evaluate the potential for geochemical methods to differentiate various contamination vectors, 538 groundwater wells from the shallow aquifer in Campanian Plain (CP) were sampled. The dataset includes both major and trace elements. Natural water-rock interactions, which primarily depend on local lithology, control the majority of geochemical parameters, including most of the major and trace elements. Using prospective statistical methods in combination with the traditional geochemical techniques, we determined the chemical variables that are enriched by anthropogenic contamination (i.e. NO3, SO4 and U) by using NO3 as the diagnostic variable for detecting polluted groundwater. Synthetic agricultural fertilizers are responsible for the majority of SO4 and U pollution throughout the CP area. Both SO4 and U are present in the groundmass of synthetic fertilizers; the uranium concentration is specifically applicable as a tracer for non-point source agricultural fertilizer contamination. The recognition of non-geological (anthropogenic) inputs of these elements has to be considered in the geochemical investigations of contaminated aquifers.

Education and training among Italian postgraduate medical schools in public health: a comparative analysis.

BACKGROUND: The postgraduate medical Schools in Public Health (locally known as School of Hygiene and Preventive Medicine) should ensure adequate scientific and technical knowledge and professional skills in preventive medicine, health promotion and healthcare planning as provided by Ministerial Decree 285/2005. The Italian Committee of Medical Residents in Hygiene, Preventive Medicine and Public Health of the Italian Society of Hygiene, Public Health and Preventive Medicine - S.It.I. (Consulta Nazionale dei medici in formazione specialistica S.It.I.) has always been engaged in monitoring activities on public health teaching, guaranteeing the homogeneity of educational proposals among all national Schools in Public Health. The purpose of this study is to provide a 'snapshot' of public health education and training in Italy and to identify the improvement actions needed for implementing an innovative and homogeneous public health training. METHODS: A cross-sectional study was carried out over a period of three months (March to May 2013). A self-administered questionnaire was e-mailed to local Committee's delegates of all 32 postgraduate medical Schools in Public Health in Italy. The questionnaire was structured in four sections: general information, University education and training, extra-University training, interdisciplinary activities. The majority of local Committee's delegates have agreed to be enrolled in the survey. RESULTS: A total of 28 questionnaires were returned (88% response rate). The number of residents in each Italian School in Public Health ranged from 7 to 31. The distribution of professors in relation to residents is not similar for each University Schools. The ratio professors/residents spanning from 0.2 to 2. About teaching, only 4 University Schools offered all courses requested by Ministerial Decree 285/2005. Most of them offered at least 75% of the requested courses, but there were Schools in which the courses were less than 50%. The vast majority of schools held more than 60% of the qualifying activities considered essential according to the Decree, while 2 Schools were below 50%. All Schools required an internship of 6-12 months in local health authority offices (ASL), mainly concerning the Department of Prevention activities. In all Schools a period of stay in a Hospital Medical Direction was scheduled, while professional activities at Residential care homes were very rarely included in training programmes. Many Schools allowed residents to attend companies with biological hazard or to follow similar activities in dedicated services of ASL. Finally, in the majority of Schools, a training period in various local (Service for Water Control), regional (Departments) or national (Ministry, National Institute of Health) health facilities was contemplated and, in some cases, also in other Universities or Research Institutes. CONCLUSIONS: Although the Ministerial Decree indicates the essential milestones of the public health education, flexibility is seen as an important element in order to optimize resources and contextualize the adequate education of residents. In any case, at least regarding public health courses, the majority of University education and extra-University training activities should be carried out by all Schools. In order to obtain shared knowledge and skills, the Ministerial Decree should be revised taking into account flexibility and changing as intrinsic characteristics of public health profession and learners should be involved in the reform to strengthening the role of public health teaching.

Integrated high-throughput analysis identifies Sp1 as a crucial determinant of p53-mediated apoptosis.

The restoration of p53 tumor suppressor function is a promising therapeutic strategy to combat cancer. However, the biological outcomes of p53 activation, ranging from the promotion of growth arrest to the induction of cell death, are hard to predict, which limits the clinical application of p53-based therapies. In the present study, we performed an integrated analysis of genome-wide short hairpin RNA screen and gene expression data and uncovered a previously unrecognized role of Sp1 as a central modulator of the transcriptional response induced by p53 that leads to robust induction of apoptosis. Sp1 is indispensable for the pro-apoptotic transcriptional repression by p53, but not for the induction of pro-apoptotic genes. Furthermore, the p53-dependent pro-apoptotic transcriptional repression required the co-binding of Sp1 to p53 target genes. Our results also highlight that Sp1 shares with p53 a common regulator, MDM2, which targets Sp1 for proteasomal degradation. This uncovers a new mechanism of the tight control of apoptosis in cells. Our study advances the understanding of the molecular basis of p53-mediated apoptosis and implicates Sp1 as one of its key modulators. We found that small molecules reactivating p53 can differentially modulate Sp1, thus providing insights into how to manipulate p53 response in a controlled way.

Radon hazard in shallow groundwaters II: dry season fracture drainage and alluvial fan upwelling.

²²²Rn concentrations have been measured in a well located on the edge of a large Pleistocene-Holocene fan and belonging to the shallow pyroclastic aquifer of the Pietramelara Plain, southern Italy. The aim of this study has been both to characterise the hydrological inputs that determine the influx of ²²²Rn to the shallow aquifer and to understand the correlations between ²²²Rn, major ions, physical-chemical parameters and rainfall. Results obtained from the time series indicate that the studied well shows a ²²²Rn variability that is inconsistent with a mechanism of pure hydrological amplification, such as described in Radon hazard in shallow groundwaters: Amplification and long term variability induced by rainfall (De Francesco et al., 2010a). On the contrary, in this well hydrological amplification appears to be mainly tied to the upwelling of alluvial fan waters, rich in radon, in response to pistoning from recharge in the carbonate substrate. This upwelling of alluvial fan waters occurs during almost the whole period of the annual recharge and is also responsible of the constant increase in ²²²Rn levels during the autumn-spring period, when both the water table level and weekly rainfall totals drop. Furthermore, a rapid delivery mechanism for ²²²Rn likely operates through fracture drainage in concomitance with the very first late summer-early autumn rains, when rainfall totals appear largely insufficient to saturate the soil storage capacity. Results obtained from this study appear to be particularly significant in both radon hazard zoning in relation to the shallow aquifer and possibly also for indoor radon, owing to possible shallow aquifer-soil-building exchanges. Moreover, both the spike-like events and the long wave monthly scale background fluctuations detected can also have potential significance in interpreting ²²²Rn time series data as seismic and/or volcanic precursors. Finally, ²²²Rn has proved to be an excellent tracer for hydrological inputs to the shallow aquifer when combined with major ions, physical-chemical data and geological and geomorphological controls.

Radon hazard in shallow groundwaters: amplification and long term variability induced by rainfall.

(222)Rn concentrations have been determined with a RAD7 radon detector in shallow groundwaters of the Pietramelara Plain, north-western Campania, southern Italy, where pyroclastic deposits, along with recent stream alluvial sediments, come in contact with Mesozoic carbonate reservoirs. The aim of this study has been to study the annual variation of (222)Rn concentration in the shallow groundwaters, scarcely considered in the literature and of obvious relevance for radon hazard evaluation. Our results definitely show that (222)Rn levels are characterized by a clear annual periodicity, strictly related to rainfall and water table levels, with a pronounced difference between the dry and the wet season. In this last case with concentrations increasing up to two orders of magnitude (up to two times the lower threshold given in the Recommendation 2001/928/EURATOM for public waters). In relation to this, experimental field data will be presented to demonstrate that this variability is due to purely hydrological mechanisms, mainly rinse out and discharge that control leaching efficiency. The detected cycle (Radon Hydrological Amplification Cycle, RHAC) has been generalized for the Mediterranean Tyrrhenian climate. The marked and seasonally persistent amplification in (222)Rn levels poses the problem of evaluating the epidemiological risk brought up by this previously not yet reported mechanism. This mechanism, occurring in shallow groundwaters, very likely should strongly influence indoor radon levels via groundwater-soil-building exchange.

Deregulated cyclin E promotes p53 loss of heterozygosity and tumorigenesis in the mouse mammary gland.

Deregulation of cyclin E expression and/or high levels have been reported in a variety of tumors and have been used as indicators of poor prognosis. Although the role that cyclin E plays in tumorigenesis remains unclear, there is evidence that it confers genomic instability when deregulated in cultured cells. Here we show that deregulated expression of a hyperstable allele of cyclin E in mice heterozygous for p53 synergistically increases mammary tumorigenesis more than that in mice carrying either of these markers individually. Most tumors and tumor-derived cell lines demonstrated loss of p53 heterozygosity. Furthermore, this tumor susceptibility is related to the number of times the transgene is induced indicating that it is directly attributable to the expression of the cyclin E transgene. An indirect assay indicates that loss of p53 function is an early event occurring in the mammary epithelia of midlactation mammary glands in which cyclin E is deregulated long before evidence of malignancy. These data support the hypothesis that deregulated expression of cyclin E stimulates p53 loss of heterozygosity by promoting genomic instability and provides specific evidence for this in vivo. Cyclin E deregulation and p53 loss are characteristics often observed in human breast carcinoma.

Efficacy of silymarin-phospholipid complex in reducing the toxicity of aflatoxin B1 in broiler chicks.

Silymarin, the standardized extract of Silybum marianum, is used as a hepatoprotector in man, and is a potent antihepatotoxic agent. This study focused on the effects of a silymarin-phospholipid complex in reducing the toxic effects of aflatoxin B1 (AFB1) in broiler chickens. Twenty-one 14-d-old male commercial broilers were randomly allotted to 3 groups and treated as follows: basal diet alone [Group C (Control)]; AFB1 at 0.8 mg/kg of feed [Group B1]; AFB1 at 0.8 mg/kg of feed plus silymarin phytosome, a silymarin complexed form with phospholipids from soy, at 600 mg/kg of BW [Group B1+Sil]. Considering the whole growth cycle, BW gain and feed intake were lower in AFB1-treated birds with respect to controls (P < 0.05). In the B1+Sil group, BW gain and feed intake were higher with respect to birds receiving AFB1 alone (P < 0.05), and not different from the control birds. Serum biochemistry showed no difference among groups, except for a decrease of alanine amino transferase (ALT) in chicks treated only with AFB1. Alanine amino transferase activity in AFB1 plus silymarin phytosome treated birds was not different from the controls. No treatment differences were noted on liver weight. In conclusion, our results suggest that silymarin phytosome can provide protection against the negative effects of AFB1 on performance of broiler chicks.

Effects of silymarin, a natural hepatoprotector, in periparturient dairy cows.

Silymarin, a natural acknowledged hepatoprotector used in humans to treat liver diseases, has been tested in dairy cows during peripartum, a period during which animals are subject to subclinical fatty liver. Ten grams of silymarin (76% pure extract consisting in flavonolignans, taxifolin, and other trace compounds) per day, was administered as a water suspension by an oral drench to 15 cows from d 10 before expected calving to 15 d after calving. Milk production was measured, and colostrum, milk, and blood samples were analyzed during the experimental period. Treated animals showed the peak of milk production at 55 +/- 1.85 d after calving, 1 wk before the control group (62 +/- 3.27 d); the average peak production was 41.6 +/- 1.05 kg for the treated group vs. 39.1 +/- 1.44 kg for the control; the treated animals maintained a greater milk production than control cows throughout lactation (9922.1 +/- 215.7 vs. 9597.8 +/- 225.4 kg). Milk composition was unaffected by treatment. No silymarin residues were detected in colostrum and all milk samples. After calving, body condition score (BCS) decrease was greater for control compared with treated cows. Glucose, urea, triglycerides (TG), total cholesterol, beta-hydroxibutyrate (BHBA), and gamma-glutamyl transferase (GGT) in plasma were unaffected by treatment. Plasma nonesterified fatty acids (NEFA) on d-7 were higher in treated cows compared with the control group (741 vs. 181 micromol/L). From this evidence, it is possible to conclude that silymarin beneficially affected lactation performances and body condition of treated animals. Blood and milk parameters do not indicate any adverse effects of feeding this natural compound.

Silymarin, a possible hepatoprotector in dairy cows: biochemical and histological observations.

Silymarin, a standardized extract from Silybum marianum seed, is a natural hepatoprotector used for the treatment of liver diseases in man. The aim of this study was to investigate its safety and efficacy in periparturient dairy cows. Ten treated and 10 control pregnant dairy cows were paired by parity, body condition score (BCS), health condition and previous milk production. Treatment consisted of daily 10 g per animal of silymarin extract administered as oral drenches, from 10 days prior to the calving date to 15 days after calving. Blood samples and liver biopsies were taken from each animal at 7 and 30 days after calving. Hepatic functions were evaluated by assay of plasma beta-hydroxybutyrate (BHBA), total cholesterol, high-density lipoproteins, low-density lipoproteins, triglyceride and total bilirubin. The histological aspect of the liver was assessed in biopsies. Clinical chemistry values were similar for both groups and effects at different times (day 7 versus day 30; P < 0.05) were attributed to physiological variations in periparturient cows. Histology showed fat accumulation in the liver of both groups, as it is expected in periparturient dairy cows. In treated cows, fat-rich hepatocytes were observed near the central vein. These observations suggest that, at the used dosage, S. marianum extract has no adverse effect on the liver of lactating cows, and presents no objective evidence for a hepatoprotective effect in this species.

First field determination of the 13C/12C isotope ratio in volcanic CO2 by diode-laser.

Carbon isotope ratio analysis using a laser-based technique has been performed in the field, on the gaseous emissions from an active volcano. We here describe that 13CO2/12CO2 determinations can be carried out in a quasi-continuous regime using a compact, selective and sensitive diode laser spectrometer at a wavelength of 2 mum. Within the Solfatara crater (near Naples, Italy), in a very harsh environment, we were able to determine relative 13CO2/12CO2 values, on the highest flux fumarole, with an accuracy of 0.5 per thousand. Regular and frequent observations of the carbon isotopes in volcanic gases, which become possible with our methodology, are of the utmost importance for geochemical surveillance of volcanoes.

[Preliminary study of the chemical characteristics of water inside and outside the area of Cassino]. / Studio preliminare sulle caratteristiche chimiche delle acque interne ed esterne dell'area di Cassino.

Quality and control of waters, particularly phreatic waters, is a strong need of a modern society and in particular of all administrations that is entitled to care for its citizen's health. The current legislation although not very strict, or at least not as strict and careful as it should be and definitely less than that of the World Health Organization (WHO), has recently constrained thresholds for maximum concentrations of chemical species dissolved into waters (anions, cations and heavy metals). Comparisons between data from water analyses collected in Cassino area and these thresholds have shown that these waters resulted of very good quality and they are not related to any source of inorganic pollution. Tap water should be preferred to mineral water usually in stores. Economically they are at least one thousands times cheaper and often can be considered of better quality.

MyoD activity upregulates E2F1 and enhances transcription from the cyclin E promoter in differentiating myoblasts lacking a functional retinoblastoma protein.

We investigated the mechanism leading to cyclin E accumulation when cultured mouse myoblasts, lacking functional Rb because of sequestration or deletion, are exposed to differentiating conditions (mitogen subtraction and cell-cell contact), which activate MyoD and normally downregulate factors involved in cell division. After excluding that stabilization might account for the observed cyclin-E mRNA accumulation, we found an induction of the cyclin-E promoter that correlated with E2F activity upregulation and depended on both MyoD activation and Rb inactivation. Analyses of the E2F1-promoter activity, in normal and Rb-deficient fibroblasts converted by MyoD, identified a MyoD function stimulating E2F1 expression. The E2F1 induction was very manifest in the Rb-/- cells, but also detectable, at the early stage of differentiation, in normal cells. Its effects, although not indispensable for myogenesis, presumably contribute to raise the concentration of Rb-E2F1 transcription-repressing complexes, since MyoD strongly induces also Rb in differentiating myocytes. The activity of an E2F1 promoter lacking the E2F sites indicated that E2F1 itself underwent self-repression by such mechanism at late stages of differentiation. In the absence of Rb, however, the induced E2F1 is left with only its activating role, reversing the normal effect of this MyoD function.

Intestinal nutrient-gene interaction: the effect of feed deprivation and refeeding on cholecystokinin and proglucagon gene expression.

We tested the hypothesis that dietary components reaching the bovine small intestine influence the expression of genes that encode the gastrointestinal neuropeptides cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The amount of digesta reaching the intestine was manipulated during the experiment by withholding feed from five heifers fitted with ruminal, duodenal, and ileal cannulas for 48 h and then subsequent refeeding. Duodenal and ileal biopsies were collected using a fiber-optic endoscope. A Northern hybridization procedure was used to evaluate changes in gene expression. Blood concentrations of CCK and GLP-1 were determined with RIA. The data indicate that CCK blood concentration and mRNA abundance decreased during the period of feed deprivation, but they returned to predeprivation values within 16 to 24 h of refeeding. The GLP-1 blood concentration also decreased during feed deprivation and returned to predeprivation values within 4 to 8 h of refeeding, despite the fact that proglucagon mRNA abundance did not change significantly during feed deprivation and refeeding. These findings provide evidence that CCK and GLP-1 are released in response to nutrients that reach the small intestine and may be involved in the physiological process of digestion and possibly play a role in regulating feed intake in ruminants.

The vascular dementia of Fabry's disease.

Fabry's disease, a rare X-linked disorder of glycosphingolipid metabolism, can present as an insidious dementia in middle or later life. This genetic disorder produces a deficiency of alpha-galactosidase A which results in the deposition of glycosphingolipids in blood vessel walls in the brain as well as in the kidney, heart, peripheral nerves, and other organs. Among the cerebrovascular manifestations of this disorder is a vascular dementia from involvement of multiple small penetrating blood vessels. Fabry's disease is a consideration in the workup of an otherwise unexplained vascular dementia, particularly in males less than 65 years of age.